Category Archives: Indiana Stem Cells

The mailings promised Life Without Pain! via stem cell injections or IVs administered in a patients own home. The allure was obvious: more than 20% of U.S. adults suffer from chronic pain.

A court exhibit from a lawsuit filed by Iowa Attorney General Brenna Bird is seen on a laptop computer May 8 in Urbandale, Iowa.

The flyers invited Iowans to free dinners across the state. Afterward, sales people traveled to potential customers homes for high-pressure pitches disguised as pre-screenings, according to prosecutors. More than 250 people signed up, paying $3,200 to $20,000 each for a total of $1.5 million. For this, a nurse practitioner came to their homes to administer injections and IVs filled with stem cells derived from umbilical cords.

Yet experts and regulators have alternately labeled such treatments as ripoffs, scams or simply unproven. In some cases, studies have documented real harm.

Last fall, Iowas attorney general sued two proprietors responsible for the mailings in her state, naming a Minnesota man who hosts a Christian entrepreneurship podcast and his Florida business partner for allegedly deceiving consumers, many of them elderly.

In bringing the lawsuit, Iowa joined attorneys general in New York, North Dakota, Georgia, Nebraska, Arkansas and Washington state who have sued businesses alleging they fraudulently promoted unproven stem cell treatments.

Stem cells have long fascinated researchers because of their ability to reproduce and, in some cases, transform into other cell types. Because of this, they are thought to hold the potential for treating many diseases and injuries.

But the FDA has approved only a handful of such therapies, and only for certain forms of blood cancer and immune system disorders. Stem cells are considered experimental for most uses, despite being marketed as a treatment for everything from autism and emphysema to sports injuries.

The FDA has repeatedly warned Americans to be wary of businesses hawking unapproved, unproven and costly stem cell therapies, which occasionally have caused blindness, bacterial infections and tumors.

In a 2020 notice, the agency expressed concern about patients being misled about products that are illegally marketed, have not been shown to be safe or effective, and, in some cases, may have significant safety issues.

Dr. Jeffrey Goldberg, chair of ophthalmology at the Byers Eye Institute at Stanford University, whose work has documented vision loss in some patients treated with cells removed from patients' own bodies, processed and reinjected, lamented that people are "desperately willing to shell out large sums of money for unproven and in some cases, explicitly sort of sham, so-called therapeutics.

Since August 2017, the FDA has issued about 30 warning letters regarding the unproven treatments.

Experts, including Dr. Paul Knoepfler, a stem cell researcher at the University of California at Davis, and Leigh Turner, a bioethicist at the University of California, Irvine, are among those who have raised alarm that such federal action is too little to regulate a U.S. industry which Turner estimated in 2021 topped 2,700 clinics.

Because states can seek substantial fines against wayward operators, Turner said their legal actions offer promise.

"If you look at them collectively, they might over time start to have an impact, he said.

The FDA offers training to attorneys general pursuing such cases. Dr. Peter Marks, director of the FDAs Center for Biologics Evaluation and Research, said federal regulators partner with state law enforcers in a shared mission.

Iowa Attorney General Brenna Bird speaks during a town hall campaign event for Republican presidential candidate Nikki Haley on May 17, 2023, in Ankeny, Iowa.

That puts people like Iowa Attorney General Brenna Bird on the front lines.

Last year, Bird brought the case over mailers offering Iowans a pain-free life, naming the now dissolved Biologics Health and Summit Partners Group, which operated under the name Summit Health Centers, as defendants. The state also sued the companies' proprietors: Rylee Meek, of Prior Lake, Minnesota, and Scott Thomas, of Thonotosassa, Florida.

Neither man claims to have any medical training. Yet over a series of free dinners across Iowa, attendees listened to their presentations about how stem cells could ostensibly repair damage linked to back or joint pain. The claims came despite an FDA warning that no such product has been approved to treat any orthopedic condition.

One testimonial featured a woman quoted as saying she had multiple sclerosis, fibromyalgia, degenerative joint problems and scoliosis. It implied the treatment worked so well she was able to stop using a walker and taking opioids. Prosecutors say that left people believing stem cells are effective at treating all the conditions listed.

The company offered packages ranging from 5 million cells to up to 60 million to fix customers' ailments. Iowas lawsuit described the practices as scattershot, for-profit experimentations.

Research has shown dead cells are often injected, Knoepfler said.

The Iowa case is still in the discovery stage, with the trial set for March 2025.

Meek and Thomas did not return multiple text and email messages from The Associated Press. Nor did their attorney, Nathan Russell, though he did rebut many of the allegations in court filings, including that the promotional information was deceptive or misleading. The filing stressed that Meek and Thomas always emphasized they were not doctors.

Instead, Meek promoted himself as the $100 million man and touted his business prowess on his Kings Council podcast. His and Thomas book, Intentional Influence in Sales: The Power of Persuasion with Neuro-linguistic Programming, is described as a way to get people to think the way you want them to think, without them even realizing it.

Nearly a quarter of Americans struggle with symptoms of depression, according to the latest Centers for Disease Control and Prevention data from an October 2023 survey. That number is down from 2020 to 2021, when the COVID-19 pandemic exacerbated mental health conditions for millions of Americans.

Like other forms of mental illness, depression impacts groups of people differently depending on their unique backgrounds and experiences. While depression is among the most common forms of mental illness, some portions of the U.S. are seeing rates of depression fall faster than others.

Northwell Health partnered with Stacker to look at which groups of people are the most likely to feel depressed, using data from the CDC.

Signs someone may have depression include an inability to focus, thoughts of death or suicide, hopelessness, and low self-worth, as well as changes in appetite and sleep patterns, according to the World Health Organization.

Depression can be transitorybrought on by the loss of a loved one or other difficult life eventsor chronic, such as for those who live with bipolar disorder. The latest data on depression rates suggest some of the uptick in depression during COVID-19 may have been more of the former.

Depression has lingered at elevated levels for some communities, including young people and those who identify as part of the LGBTQ+ community.

Americans ages 18 to 29 years old report the highest levels of depression, with those 30 to 49 years old showing the next highest levels, according to the CDC. Rates of depression taper off even more as Americans clear the age of 60.

Higher reported rates of depression in young people could partially be attributed to the way each generation views mental illness. Members of Gen Z, those born between 1997 and 2012, have been more open to talking about mental illness and seeking therapy, for example, than older generations who came of age at a time when mental health disorders were heavily stigmatized in media and popular culture.

Surveys have found that discrimination is often cited as a significant source of stress; Black and Hispanic adults, specifically, report higher levels of stress from discrimination compared to their white peers.

When it comes to depression rates, a similar trend appears. Hispanic, multiracial, and Black Americans report elevated rates of depression compared to white Americans, according to the latest survey data the CDC collected in late 2023.

Furthermore, LGBTQ+ Americans have reported higher levels of stress and mental illness compared to straight, cisgender people. Transgender individuals are also more than six times as likely to attempt suicide, according to a Swedish study published in The American Journal of Psychiatryone of the only studies to compile such data for an entire country over a 10-year period.

The current rates of depression among more vulnerable groups are particularly concerning at a time when mental health professionals are struggling to meet a higher demand for mental health care services.

Story editing byShannon Luders-Manuel. Copy editing by Tim Bruns.

This story originally appeared on Northwell Health and was produced and distributed in partnership with Stacker Studio.

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Experts: Don't believe everyone who is hawking stem cells - The Times of Northwest Indiana

INDIANAPOLIS (WISH) The Be the Match marrow registry has more than 39 million people signed up and willing to donate bone marrow or stem cells to those with blood cancers or other diseases, but the chances of find a match drop significantly for non-white patients.

Tarita Gibson with Be the Match said, The gap is for African-Americans 29% youll find a donor on the registry to 79% of Caucasian will find a donor on the registry.

For Asian or Pacific Islander patients, there is a 47% chance of finding a match. Hispanic patients have a 48% chance of finding a match while there is a 60% chance for Native-Americans. Gibson said because donors and patients need to share a similar genetic background to match, they need more diversity on the list to save lives.

Gibson said, We want to have equal outcomes for all ethnic backgrounds, so its very important for people between the ages of 18-40 to join the registry, [and] get some education about the registry.

One local doctor said donating bone marrow requires a minor surgical procedure and stem cell donation is similar to donating blood.

Dr. Yogesh Jethava, a Medical Oncologist at Indiana Blood and Marrow Transplantation, said, The blood comes out of here, goes into the machine, the machine takes the stem cells, we call them mononuclear cells, they are taken out, and the rest of the blood is pushed back in you.

Joining the registry is even easier. All you have to do is request a kit to your house, swab your mouth and send it back, then you are placed on a list and could be matched with anyone in the United States. This is important because family members are often not a match.

Jethava explained, DNA is made up of four different strands and there is no garuntee that me and my brother will inherit exactly the same half from the parents.

Be the Match is working to expand the registry with continued outreach and education.

We do a lot of awareness events where people come to get awareness and learn what its all about, Gibson said. We educate groups all the time, student groups, organizations, corporations, we really need more donors on the registry.

You can join the bone marrow registry be signing up here.

Continue reading here:
Diversifying marrow registry critical to achieve medical equity say advocates - WISH TV Indianapolis, IN

By Catholic News Service Posted December 23, 2021

The following editorial was published online Dec. 17 by Our Sunday Visitor, a national Catholic newsweekly based in Huntington, Indiana. It was written by the editorial board.

***

This time last year, when we flipped the calendar from 2020 to 2021, many glasses were raised to toast what we all hoped would be a better year ahead. 2020 was so difficult for so many. Too many of us saw sickness and death up close as we mourned the loss of 350,000 people in the United States who had died from COVID-19 mothers and fathers, sisters and brothers, grandparents, aunts, uncles, friends and so many more.

We sheltered in place and longed for the physical closeness that we had previously taken for granted. Our beloved Masses were canceled in order to protect ourselves and our neighbors, especially our elderly brothers and sisters and others who were significantly vulnerable to the virus.

We masked up, washed our hands and socially distanced, hoping that these small sacrifices might help to flatten the curve and ease the overwhelming burden that had been placed on our health care workers the doctors and nurses and others who Pope Francis called the unsung heroes of this pandemic.

Aside from masking and washing and distancing, there was little we could do other than pray that God would lead us out of the darkness. Even amid our suffering, we can be confident that he hears our cries, as Scripture assures us. When you call me, and come and pray to me, I will listen to you (Jer 29:12-13). In the Gospel of Matthew, Jesus himself says, Ask and it will be given to you; seek and you will find; knock and the door will be opened to you (7:7-8).

In the twilight days of 2020, that door was opened. After months of research and trials, scientists and medical researchers produced a number of vaccines that were approved for emergency use by the public, and on Dec. 11, 2020, the vaccine rollout began a stunning, unprecedented success by the scientific community.

Ten days after the first doses were given in the United States, on Dec. 21, 2020, the Vaticans Congregation for the Doctrine of the Faith attempted to put to rest growing concerns over the use of fetal stem cells in the development of the vaccines, ruling not only that the use of the approved vaccines was morally licit but that the morality of vaccination depends not only on the duty to protect ones own health, but also on the duty to pursue the common good. Pope Francis and the U.S. bishops called receiving the vaccine an act of love.

With vaccination medically and morally approved, it seemed likely that COVID-19 would largely be snuffed out in 2021. Optimism abounded, and by mid-April, a quarter of the U.S. population was fully vaccinated; we reached 50% by the end of July. Since then, progress has stalled as of mid-December, just 60% of Americans are fully vaccinated and the consequences have been dire.

After tragically losing 350,000 people to COVID in 2020, 450,000 more people were killed by the virus in 2021 an almost unfathomable amount considering that an effective vaccine is available. Sadly, the data makes it clear that the vast majority of COVID-19 deaths in 2021 were preventable. According to the Centers for Disease Control and Prevention, those who are fully vaccinated are more than 10 times less likely to be hospitalized or die from COVID-19.

Some would argue that the rise in breakthrough cases those who contract the virus despite being fully vaccinated is evidence that the vaccines are ineffective. No vaccine is 100% effective in preventing contraction of a virus or disease; its effectiveness lies in the ability to ward off serious symptoms that lead to hospitalizations and death, as the statistics above show.

As new variants such as omicron spread, and more time passes since the vaccine was received, breakthrough cases will continue to rise. This is why health care professionals are urging those who qualify to get a booster shot something that our culture doesnt see as controversial when it protects us against tetanus or shingles or hepatitis or myriad other maladies.

Perhaps well need a yearly COVID-19 booster just as we have annual flu shots. If it protects us from serious illness or worse it seems well worth it.

The same can be said for the vaccine itself. Its time for those who are unvaccinated to stop moving the bar. First, it was a moral objection, one that the CDF, the U.S. bishops and the pope himself have cleared up. Then came the claim that there was not enough data to prove that the vaccine is safe and effective; study after study has shown those concerns were unfounded. The next complaint was that the vaccines were only approved on an emergency basis; that, too, is no longer the case.

The science is sound, and the numbers tell the story. Of the 450,000 people who have died this year, how many could have been saved had they received the vaccine?

For centuries, critics of the Catholic faith have argued that the church is anti-science. They couldnt be further from the truth. Toward the end of the Second Vatican Council, Pope St. Paul VI spoke to men of thought and science, telling them, Never perhaps, thank God, has there been so clear a possibility as today of a deep understanding between real science and real faith, mutual servants of one another in the one truth.

Todays truth is simple: The COVID-19 vaccine is a gift. If we accept it, we honor the churchs teaching that calls us to protect all human life. If we continue to reject it, we must ask: What will the death toll be when we flip the calendar again?

***

The views or positions presented in this or any guest editorial are those of the individual publication and do not necessarily represent the views of CatholicPhilly.com, Catholic News Service or the U.S. Conference of Catholic Bishops.

More:
COVID-19 vaccine is a gift that is saving lives - CatholicPhilly.com

Amanda is a retired educator with many years of experience teaching children of all ages and abilities in a wide range of contexts.

The cell membrane is a fluid, semi-permeable barrier which not only protects the interior of the cell but controls the movement of substances in and out.

William Cochot CC BY-SA 4.0 via Wikimedia Commons

Two main methods by which organisms move materials around inside their bodies are important for an understanding of cellular transport:

The movement of substances in and out of cells (nutrients in and toxins out, for example) is a very important part of biology as without it no cell and so no organism could live very long. Substances can only cross the protective cell membrane by diffusion, osmosis or active transport (don't worry - these terms will all be explained shortly). Mass flow only works at the organ, tissue and whole organism level.

You probably already know that all matter is made up of tiny, invisible atoms. When atoms become linked together, they form molecules. Both atoms and molecules can develop an electrical charge. Electrically charged atoms or molecules are called ions.

In biology, we use the simple term particles to refer to all of these things: atoms, molecules and ions.

It is these particles that move within and between cells by diffusion, osmosis or active transport. Particles can only be moved in out of cells when they are dissolved in water. Water with particles dissolved in it is known as a solution. The water in a solution is called the solvent and the particles are called the solute. We will come back to these terms later.

So that you can easily check your understanding, there's a fun quiz to do at the end. All the answers can be found on this page and you'll get your score straight-away.

The classic definition of diffusion is the movement of a substance from an area of higher concentration to an area of lower concentration (the concentration gradient). But what does that actually mean?

Particles are always in random motion. Concentration simply means how many particles there are in a given volume. By random motion, particles will naturally spread out from where there are lots of them to where there are few or none. This is what we mean by diffusion along the concentration gradient.

Watch this short animation to better understand this idea:

Two conditions must be met for a substance to enter a cell by diffusion.

Oxygen is an excellent example of a substance vital to life which enters cells by the process of diffusion. Oxygen is consumed by cells in the process of respiration. This means that the concentration of oxygen in any given cell is likely to decrease. This creates a concentration gradient which draws new oxygen into the cell by diffusion across the cell membrane.

The process of diffusion along a concentration gradient can also operate to move substances out of cells. An excellent example of this is the case of carbon dioxide. Carbon dioxide is a by-product of respiration. Consequently, carbon dioxide tends to increase in concentration in cells. Molecules of carbon dioxide exit the cell by diffusion once the concentration of the substance inside the cell is higher than it is outside the cell.

In both of these examples, the particles that make up the substance are moving down a concentration gradient: from an area of higher concentration to an area of lower concentration.

Diffusion in itself is generally a very slow process. Sometimes cells need to move substances more quickly and so a number of mechanisms have evolved to speed diffusion up.

These mechanisms use three key factors:

Let's look at each in turn.

You probably already know that when the temperature of a substance increases (it gets hotter) the particles that compose the substance start to move around a lot faster. This increase in movement when substances warm up can also help propel diffusion as the particles get going at a quicker rate.

Scientific Temperatures

In biology and the other sciences, temperature is always measured and expressed in C (degrees Celsius) and not in Fahrenheit, which you may be more familiar with at home.

Humans are "warm-blooded" animals or more properly, endotherms. This means that we can maintain a steady internal temperature. In our case this is about 37C and maintains our metabolism even when it is cold in the environment. All mammals are endothermic. Most reptiles, however, are exotherms, or "cold-blooded" and have to shut down if the environmental temperature falls below a certain level.

The larger a cell's surface area, quicker the movement of substances in and out. This is simply because there is more membrane for the substances to cross over. You can imagine the cell as a room, perhaps. If the doorway is wide, more people can walk in or out together. If the doorway is narrow, fewer people can come in and out at any one time.

But having a big surface area alone doesn't necessarily speed up diffusion. That large surface area has to be in a certain ratio to the internal volume of the cell. Sounds complicated? It does sound that way, but don't worry, it's actually fairly easy to grasp.

Being small and spherical helps cells to maintain a good volume to surface area ratio. Other adaptations include 'wobbly' membranes and flattening, all of which increase surface area and therefore the cell's ability to absorb substances by diffusion.

Ruth lawson CC BY-SA 3.0 via Wikimedia Commons

The most important factor for a cell is not just its surface area, but the surface area to volume ratio. The consumption rate of substances is dependent upon volume, but it is the cell membrane's surface area that determines the rate of absorption of new material.

In other words, the greater the surface area of the cell compared to its volume, the more efficient the cell will be in performing its functions.

It is interesting to note that as a cell gets bigger, its volume will increase more than its surface area. Let's look at what happens if you double the size of a cell:

So you can see that there is a negative relationship between size and efficiency in cells. The bigger they get the more difficult it is for them to take up materials fast enough.

There are three key ways by which a cell can increase its surface area to volume ratio.

Diffusion across the cell membrane happens because of the concentration gradient between the intracellular and extracellular environments.

Openstax Biology [CC BY-SA 4.0]

We have already seen that diffusion means the movement of substances from areas of high concentration to areas of low concentration.

However, the rate of diffusion is dependent upon the concentration gradient. The concentration gradient is calculated as the difference in concentration per centimeter.

Imagine a boy rolling a ball down a hill. If the hill is very steep, the ball will roll faster. If a concentration gradient is steep, that is to say it represents a rapid change from high concentration to low concentration, then substances will move down it faster - just like the ball!

A typical cell membrane is very thin. The reason for this is to keep the distance between internal and external concentrations short. This helps create a steeper concentration gradient, enabling the movement of substances in and out of the cell.

When you take a deep breath, the concentration of oxygen in the lungs is increased. The lungs are full of air with a high oxygen concentration compared to a lower oxygen concentration in the blood. Therefore, oxygen diffuses into the bloodstream.

The movement of substances in and out of the cell by diffusion is known as passive transport. However, sometimes substances will not diffuse across the membrane and need to be chemically assisted. This is known as active transport.

A typical situation in which active transport is required is when a substance must travel against the concentration gradient. Clearly in this case diffusion will not help at all!

Active transport always occurs across the cell membrane and it requires an input of extra energy to push the particles up the concentration gradient. The energy for active transport is provided by the process of respiration.

The cell membrane has specialised molecules incorporated into it. These carrier molecules absorb the energy of respiration in order to assist other substances in crossing the cell membrane.

Osmosis is exactly the same mechanism as diffusion but it is a term used to apply specifically to the movement of water molecules. So when water molecules (H2O) are transferred across a partially permeable membrane from an area of higher to an area of lower concentration, which is called osmosis.

Let's just pause here a moment to give some definitions of a few important terms we've used:

Something to think about...

Biologists will often refer to a solution which contains a large amount of solute as having a 'concentrated solution' but you can also think of that as a solution with a low concentration of water molecules. So the concept of high and low concentration is always relative to the molecules you are referring to!

An animal cell is surrounded by a partially permeable membrane. Because osmosis enables water to flow so freely through the cell system, it can do a lot of harm as well as good. The greatest danger is that of lysis.

A complex of chemical mechanisms ensures that, in a healthy animal, the tissue fluid surrounding the cells is maintained at an equal concentration to that of the cytoplasm.

Osmosis is far less of a threat to plant cells than to animal cells. In fact, they have evolved a rigid cell wall which enables them to use osmosis to their advantage.

Water enters a plant cell by osmosis when the cytoplasm has a lower concentration of water molecules than the surrounding aqueous environment. The cell expands to accommodate the influx of water molecules. This stretches the cell's wall. As we have seen with an animal cell, the membrane is not sufficiently strong to resist too much expansion and can burst, resulting in the cell's death. A plant's cell wall, however, is much stronger and as the cell fills with water, it exerts an opposite pressure until equilibrium is reached and no more water can enter. A plant cell in this state, full to capacity with water molecules, is called turgid.

This process is vital for plants. Turgid cells push tightly together and enable the plant to remain upright and hold its leaves towards the light.

When a plant wilts, or becomes flaccid, it is because of a lack of water. It can no longer absorb sufficient water molecules by osmosis to sustain its turgidity, so the leaves and possibly also the stem lose their main support.

If this condition is acute and prolonged, the vacuole in the plant cell's core, where water and nutrients are stored, can dry out, causing the cytoplasm to shrivel away. A plant in that condition is clearly dying. Its cells are referred to as being plasmolyzed.

Here is a bullet point summary of what we have learned on this page:

For each question, choose the best answer. The answer key is below.

If you got between 0 and 1 correct answer: A good attempt, but some revision might be worthwhile to improve your score.

If you got between 2 and 3 correct answers: You've grasped all the basics - well done! A bit of revision would help consolidate your knowledge.

If you got 4 correct answers: That's a great score - well done!

If you got 5 correct answers: Fantastic result! You have a good understanding of all the material. Excellent!

2015 Amanda Littlejohn

Amanda Littlejohn (author) on April 01, 2016:

Hi Alexis!

Thank you so much for your comment. Sorry it has taken me so long to reply, but I have only just received my notifications. Seems there was a glitch on some hubs.

I'm glad you enjoyed this biology article and I hope you find it useful for your son.

Bless you 🙂

Ashley Ferguson from Indiana/Chicagoland on February 18, 2016:

I loved biology as a child. Thank you for providing a child-friendly hub for my my son one day. 🙂 Hope to see you around in the hubs.

Amanda Littlejohn (author) on January 06, 2016:

Hi Shelley!

Thanks for your comment - I'm glad you enjoyed it. 🙂

FlourishAnyway from USA on December 06, 2015:

Excellent educational hub. Very thorough and well researched!

More here:
Biology for Kids: The Movement of Substances in and out of ...

Stem cell laws and policy in the United States have had a complicated legal and political history.

Stem cells are cells found in all multi-cellular organisms. They were isolated in mice in 1981, and in humans in 1998.[1] In humans there are many types of stem cells, each with varying levels of potency. Potency is a measure of a cell's differentiation potential, or the number of other cell types that can be made from that stem cell. Embryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst. These stem cells can differentiate into all other cells in the human body and are the subject of much scientific research. However, since they must be derived from early human embryos their production and use in research has been a hotly debated topic.

Stem cell treatments are a type of cell therapy that introduce new cells into adult bodies for possible treatment of cancer, diabetes, neurological disorders and other medical conditions. Stem cells have been used to repair tissue damaged by disease or age.[2] Cloning also might be done with stem cells. Pluripotent stem cells can also be derived from Somatic cell nuclear transfer which is a laboratory technique where a clone embryo is created from a donor nucleus. Somatic cell nuclear transfer is also tightly regulated amongst various countries.

Until recently, the principal source of human embryonic stem cells has been donated embryos from fertility clinics. In January 2007, researchers at Wake Forest University reported that "stem cells drawn from amniotic fluid donated by pregnant women hold much of the same promise as embryonic stem cells."[1]

In 2000, the NIH, under the administration of President Bill Clinton, issued "guidelines that allow federal funding of embryonic stem-cell research."[1]

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos.[3] In 1995, the NIH Human Embryo Research Panel advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel's recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,[4] but did agree to fund research on left-over embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed the DickeyWicker Amendment in 1995 (the final bill, which included the Dickey Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo. In 1998, privately funded research led to the breakthrough discovery of human Embryonic stem cells (hESC).

No federal law ever did ban stem cell research in the United States, but only placed restrictions on funding and use, under Congress's power to spend.[5]

In February 2001, George W. Bush requested a review of the NIH's guidelines, and after a policy discussion within his circle of supporters, implemented a policy in August of that year to limit the number of embryonic stem cell lines that could be used for research.[1] (While he claimed that 78 lines would qualify for federal funding, only 19 lines were actually available.[1])

In April 2004, 206 members of Congress, including many moderate Republicans, signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported.

In May 2005, the House of Representatives voted 238-194 to loosen the limitations on federally funded embryonic stem-cell research by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors despite Bush's promise to veto if passed. [2] On July 29, 2005, Senate Majority Leader William H. Frist (R-TN), announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[6] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill, 63-37, which would have made it legal for the Federal government to spend Federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures. On July 19, 2006 President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.

The National Institutes of Health has hundreds of funding opportunities for researchers interested in hESC.[7] In 2005 the NIH funded $607 million worth of stem cell research, of which $39 million was specifically used for hESC.[8]

During Bush's second term, in July 2006, he used his first Presidential veto on the Stem Cell Research Enhancement Act. The Stem Cell Research Enhancement Act was the name of two similar bills, and both were vetoed by President George W. Bush and were not enacted into law. New Jersey congressman Chris Smith wrote a Stem Cell Therapeutic and Research Act of 2005, which was signed into law by President Bush. It provided $265 million for adult stem cell therapy, umbilical cord blood and bone marrow treatment, and authorized $79 million for the collection of cord blood stem cells.

By executive order on March 9, 2009, President Barack Obama removed certain restrictions on federal funding for research involving new lines of human embryonic stem cells.[9] Prior to President Obama's executive order, federal funding was limited to non-embryonic stem cell research and embryonic stem cell research based upon embryonic stem cell lines in existence prior to August 9, 2001. Federal funding originating from current appropriations to the Department of Health and Human Services (including the National Institutes of Health) under the Omnibus Appropriations Act of 2009, remains prohibited under the DickeyWicker Amendment for (1) the creation of a human embryo for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero.

In a speech before signing the executive order, President Obama noted the following:

Today, with the Executive Order I am about to sign, we will bring the change that so many scientists and researchers; doctors and innovators; patients and loved ones have hoped for, and fought for, these past eight years: we will lift the ban on federal funding for promising embryonic stem cell research. We will vigorously support scientists who pursue this research. And we will aim for America to lead the world in the discoveries it one day may yield.[10]

In 2011, a United States District Court "threw out a lawsuit that challenged the use of federal funds for embryonic stem cell research."[11] The decision was a case on remand from the United States Court of Appeals for the District of Columbia Circuit.[11][12]

S1909/A2840 is a bill that was passed by the New Jersey legislature in December 2003, and signed into law by Governor James McGreevey on January 4, 2004, that permits human cloning for the purpose of developing and harvesting human stem cells. Specifically, it legalizes the process of cloning a human embryo, and implanting the clone into a womb, provided that the clone is then aborted and used for medical research. Missouri Constitutional Amendment 2 (2006) (Missouri Amendment Two) was a 2006 law that legalized certain forms of embryonic stem cell research in the state.

California voters in November 2004 approved Proposition 71, creating a US$3 billion state taxpayer-funded institute for stem cell research, the California Institute for Regenerative Medicine. It hopes to provide $300 million a year. However, as of June 6, 2006, there were delays in the implementation of the California program and it is believed that the delays will continue for the significant future. [3] On July 21, 2006, Governor Arnold Schwarzenegger (R-Calif.) authorized $150 million in loans to the Institute in an attempt to jump start the process of funding research.[13]

Several states, in what was initially believed to be a national migration of biotech researchers to California,[14] have shown interest in providing their own funding support of embryonic and adult stem cell research. These states include Connecticut [4], Florida, Illinois, Massachusetts [5], Missouri, New Hampshire, New York, Pennsylvania, Texas [6] [7], Washington, and Wisconsin.

Other states have (or have shown interest in) additional restrictions or even complete bans on embryonic stem cell research. These states include Arkansas, Iowa, Kansas, Louisiana, Nebraska, North Dakota, South Dakota, and Virginia. (States play catch-up on stem cells, USA Today, December 2004) Arkansas, Indiana, Louisiana, Michigan, North Dakota and South Dakota have passed laws to "prohibit the creation or destruction of human embryos for medical research."[5]

Policy stances on stem cell research of various political leaders in the United States have not always been predictable.

As a rule, most Democratic Party leaders and high-profile supporters and even rank and file members have pushed for laws and policies almost exclusively favoring embryonic stem cell research.[16] President Bill Clinton supported the NIH's guidelines in 2000.[1] Both the major candidates in 2008 had supported the 2005 and 2007 bills, in particular Hillary Rodham Clinton, Bill Clinton's First Lady, then U. S. Senator for New York,[17] and Barack Obama, then U.S. Senator for Illinois, who promised to sign the EFCA into law, and was a cosponsor of such bills.[18] Massachusetts governor Deval Patrick is also a proponent of embryonic stem cell research. There have been some Democrats who have asked for boundaries be placed on human embryo use. For example, Carolyn McCarthy has publicly stated she only supports using human embryos "that would be discarded".[19][20]

The Republicans largely oppose embryonic stem cell research in favor of adult stem cell research which has already produced cures and treatments for cancer and paralysis for example, but there are some high-profile exceptions who offer qualified support for some embryonic stem cell research.[5] Prominent Republican leaders against embryonic stem cell research include Sarah Palin, Jim Talent, Rick Santorum, and Sam Brownback.[5] In July 2001:

Sen. Bill Frist (R-TN) and Sen. Orrin Hatch (R-UT), a vocal abortion opponent, call[ed] for limited federal funding for embryonic stem-cell research.... House Speaker Dennis Hastert (R-IL) and other Republican House leaders [came] out in opposition to federal funding for embryonic stem cell research.

2008 GOP Presidential Candidate John McCain was a member of The Republican Main Street Partnership, and supported embryonic stem cell research,[5] despite his earlier opposition.[21] In July 2008 he said, "At the moment I support stem cell research [because of] the potential it has for curing some of the most terrible diseases that afflict mankind."[22] In 2007, in what he described as "a very agonizing and tough decision," he voted to allow research using human embryos left over from fertility treatments.[23] Former First Lady Nancy Reagan and Senator Orrin Hatch also support stem cell research, after first opposing the issue.[5] Former Senator Frist also supports stem cell research, despite having initially supported past restrictions on embryonic stem cell research. 2008 V.P. candidate Palin opposed embryonic stem cell research, which she said causes the destruction of life, thus this research is inconsistent with her pro-life position and she does not support it.[24]

A few moderates or Libertarians support such research with limits. Lincoln Chafee supported federal funding for embryonic stem cell research. Ron Paul, a Republican congressman, physician, and Libertarian and Independent candidate for President, has sponsored much legislation, and has had quite complex positions.

Several studies have examined the impact of changing funding policies on scientific research in the US and the development of new cell therapies by industry. For example, studies have highlighted an immediate and sizable drop in research productivity of US-based researchers as compared to researchers based elsewhere during the years after the enactment in August 2001 of federal funding restrictions on research involving new embryonic stem cell lines.[25][26][27][28] US knowledge production in the human embryonic stem cell field fell 35 to 40 per cent below anticipated levels, and measured in terms of forward citations to core research publications in the field, US-based follow-on work in the human embryonic stem cell research field declined by nearly 59 per cent relative to non-US-based research over the period 2001-2003.[25] During this period US based firms were also less likely to launch new therapeutic product development projects in the cell therapy field than firms outside the US, and were more likely to discontinue clinical trials for new cell therapies that were already under way.[29] All these effects were reversed as the funding environment for stem cell research in the US became more favourable during the second half of the 2000s.

In 2005, the United States National Academies released its Guidelines for Human Embryonic Stem Cell Research. These Guidelines were prepared to enhance the integrity of human embryonic stem cell research in the public's perception and in actuality by encouraging responsible practices in the conduct of that research. The National Academies has subsequently named the Human Embryonic Stem Cell Research Advisory Committee to keep the Guidelines up-to-date.[30]

The guidelines preserve two primary principles. First, that hESC research has the potential to improve our understanding of human health and discover new ways to treat illness. Second, that individuals donating embryos should do so freely, with voluntary and informed consent. The guidelines implement executive order 13505, and apply to hESC research receiving funds from the NIH. The guidelines detail safeguards to protect donating individuals by acquiring informed consent and protecting their identity. In addition, the guidelines contain multiple sections applying to embryos donated in the US and abroad, both before and after the effective date of the guidelines.[31]

The NIH guidelines define which hESC research is eligible to receive NIH funding through a series of regulations which applicants for funding must adhere to. Applicants proposing research, may use stem cell lines that are posted on the NIH registry, or may submit an assurance of compliance with section II of the guidelines. Section II is applicable to stem cells derived from human embryos.[31]

For the purposes of section II of the NIH guidelines, the following requirements must be met. First, the hESCs should have been derived from embryos created using an in vitro fertilization procedure for reproductive purposes, and no longer needed for this purpose. Second, the donors who sought reproductive treatment have given written consent for the embryos to be used for research purposes. Third, all written consent forms and other documentation must be provided.[31]

Documentation must be provided regarding the following: All options available to the healthcare facility regarding the embryos in question were explained to the individual who sought reproductive treatment. No payments of any kind may be offered for the donated embryos. Policies and procedures must be in place at the facility where the embryos were donated to ensure that neither donation nor refusal to donate affects quality of care received by the patient.[31]

There must also be a clear distinction between the donor's decision to create embryos for reproductive purposes, and the decision to donate embryos for research. This is ensured through a number of regulations which follow. First, the decision to create embryos for reproductive purposes must have been made without the influence of researchers proposing usage for the embryos to derive hESCs for research purposes. Consent for the donation of embryos should have been given at the time of donation. Finally, donors should have been informed that they have the right to withdraw consent at any time until derivation of stem cells from the embryo, or until the identity of the donor can no longer be linked to the embryo.[31]

When seeking consent from the donor, they must be informed of what will become of their donation. The donor must be informed that the embryonic stem cells would be derived from the embryos from research purposes. The donor must also be informed of the procedures that the embryo would undergo in the derivation process, and that the stem cell lines derived from the embryo may be kept for many years. In addition, the donors must be informed that the donation is not made with direction regarding the intended use of the derived stem cells, and the research is not intended to provide direct medical benefit to the donor. The donor is also to be informed that there may be commercial potential resulting from the research performed, and that the donor is not to benefit from commercial development as a result of the donation. The donor is also to be notified if information that could disclose their identity will be available to the researchers.[31]

Applicants seeking to use stem cell lines established before the effective date of the guidelines may use lines published on the NIH registry, or establish eligibility by complying with the requirements listed above. Alternately, researchers may submit materials to a working group of the Advisory Committee to the Director. The working group will review submitted materials and submit recommendations to the Advisory Committee, which will in turn make recommendations to the NIH director. A final decision regarding eligibility for funding is then made by the NIH director.[31]

The materials submitted to the working group must demonstrate that the stem cells were derived from embryos created for reproductive purposes, and are no longer needed. Also, the materials must demonstrate that the stem cells were donated by donors who had granted voluntary written consent.[31]

Research ineligible for NIH funding as dictated within the guidelines include research in which hESCs are introduced into non-human primate blastocysts. Research of the breeding of animals where hESCs may contribute to the germ line are similarly ineligible. NIH funding of the derivation of stem cells from human embryos is prohibited by the annual appropriations ban on the funding of human embryo research. Research using hESCs derived from other sources is also not eligible for funding.[31]

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Stem cell laws and policy in the United States - Wikipedia

Wei Wu and Xiao-Ming Xu (Credit: IU School of Medicine)

Researchers at Indiana University School of Medicine (Indianapolis, USA) have announced the successful reprogramming of a glial cell type in the central nervous system into new neurons in order to promote recovery after spinal cord injuryrevealing an untapped potential to leverage the cell for regenerative medicine.

This is the first time that scientists have reported modifying a NG2 gliaa type of supporting cell in the central nervous systeminto functional neurons after spinal cord injury, saidWei Wu, research associate in neurological surgery at IU School of Medicine and co-first author of the paper, which was published in the Cell Stem Cell journal.

Wu andXiao-Ming Xu, the Mari Hulman George professor of Neuroscience Research at IU School of Medicine, worked on the study with a team of scientists from the University of Texas Southwestern Medical Center.

Spinal cord injuries affect hundreds of thousands of people in the United States, with thousands more diagnosed each year. Neurons in the spinal cord dont regenerate after injury, which typically causes a person to experience permanent physical and neurological ailments.

Unfortunately, effective treatments for significant recovery remain to be developed, Xu said. We hope that this new discovery will be translated to a clinically relevant repair strategy that benefits those who suffer from a spinal cord injury.

When the spinal cord is injured, glial cells, of which there are three typesastrocyte, ependymal and NG2respond to form glial scar tissue.

Wu added: Only NG2 glial cells were found to exhibit neurogenic potential in the spinal cord following injury in adult mice, but they failed to generate mature neurons. Interestingly, by elevating the critical transcription factor SOX2, the glia-to-neuron conversion is successfully achieved and accompanied with a reduced glial scar formation and increased functional recovery following spinal cord injury.

The researchers reprogrammed the NG2 cells from the mouse model using elevated levels of SOX2a transcription factor found inside the cell thats essential for neurogenesisto neurons. This conversion has two purposes, Xu said: to generate neurons to replace those lost due to a spinal cord injury and reduce the size of the glial scars in the lesion area of the damaged tissue.

This discovery, serves as an important target in the future for potential therapeutic treatments of spinal cord injury, adds Wu, who goes on to note that such a collaboration will be continued between the two laboratories to address neuronal remodelling and functional recovery after successful conversion of glial cells into functional neurons in future.

Link:
IU School of Medicine researchers discover new potential for functional recovery after spinal cord injury - Spinal News International

At the Indiana Stem Cell Treatment Center, we provide stem cell therapy care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. The Center utilizes a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by liposuction on the same day. Stem cell therapy patients are evaluated by a respective member of our multi-specialty expert panel of Board Certified physicians representing many medical fields. The Indiana Stem Cell Treatment Center emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine. When it comes to stem cell therapy centers we always put the patients needs first

Founded in 2010 for the investigational use of stem cells deployments for degenerative conditions, the source of the cells is actually stromal vascular fraction, which is a protein rich segment of processed adipose tissue. Stromal vascular fraction contains a mononuclear cell line (predominantly autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important growth factors that turn on the stem cells and promote their activity. We have high numbers of viable cells and we are trying to learn which diseases respond best and which deployment methods are most effective. We are growing and continue to use our surgical methods to deploy SVF for various degenerative conditions. We employ a clinical research coordinator to protect our valuable data and our vision is to perfect our treatments and ultimately teach them to other physicians around the world.

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Stem Cell Treatment Centers - Indiana Stem Cell | Call Today

Umbilical cord stem cells are a type of cell called Mesenchymal (MCS). MSCs have the ability to migrate and target specic tissues. This property called homing is an event that allows cells to migrate from a remote area in the body to nd a damaged organ or tissue in a specic site. This is the mechanism by which MSCs are infused intravenously and reach the aected areas of the body to perform its regenerative functions. MCS with Whartons Jelly is the most potent of stem cells.

The cord blood is processed in such a way that all blood components associated with rejection are removed. When these growth factors, proteins, regenerative cells, and stem cells are injected into a damaged joint, they go to work to repair the source of pain. IL-1ra (Interleukin-1 receptor antagonist) immediately begins reducing the damaging inflammatory components (Tumor necrosis factor-alpha, Interferon-gamma, ect.

Call our regenerative medicine team atIndiana Medical Center for Joint Restoration and Regenerative Medicinelocated in Bloomington for more information about stem cell therapy.Other than the umbilical cord, common sources of stem cells include bone marrow or fat harvested from the patients body. Depending on the health and age of the individual, these cells may be less potent than needed, and the extraction process more invasive.

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Stem Cell Therapy | Indiana Medical Center

The situation was dire. As the pandemic raged in March, some Covid-19 patients in Milan were going into septic shock, and their blood pressure was perilously low.

A California drug company wanted to ship emergency medication to those patients, but commercial flights to Italy had been drastically scaled back. So it called PCI Pharma Services, a Philadelphia company that specialises in packaging and shipping drugs around the world. It took nearly a week, but PCI secured permits and arranged for courier jets, drivers and trains to deliver the drugs to Milan.

That day when the drug arrived, six people were saved, said Salim Haffar, PCIs chief executive.

As countries prepare to distribute hundreds of millions of Covid-19 vaccines some of which require storage as cold as the South Pole in winter and meticulous handling the highly specialised operations of companies like PCI Pharma are in heavy demand. And Wall Street, which likes nothing better than a hot trade with the potential for big profits, is rushing to grab a piece of the action.

Investors were already snapping up shares of vaccine-makers like Moderna and Pfizer, whose vaccine, developed with BioNTech, was introduced in the United States on Monday and requires an exceptionally low storage temperature of minus 70 Celsius (minus 94 degrees Fahrenheit). FedEx and UPS, whose shares have already risen this year as the pandemic forced millions to rely on online shopping, could benefit further from their roles in vaccine delivery.

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But in recent months, private equity firms and wealthy individual investors have also been seizing on smaller companies like PCI Pharma, whose cold-storage operations will play a crucial role in delivering Covid vaccines to the public.

Until recently, the temperature-controlled storage and shipping of pharmaceutical products, known as the cold chain, was a relatively sleepy corner of the health care industry. The technology to preserve animal-based cells and tissues by transporting them in cold conditions has been available since the 1950s, and certain breakthroughs in cancer research in the last decade increased demand for cold-chain transportation.

But the virus, and the temperature-sensitive vaccines that are poised to combat it, have brought new attention to the cold-chain delivery systems in the United States and beyond. Even Saturday Night Live featured a cooler full of vaccines during a recent episode.

The companies getting attention from Wall Street are notable for how niche their operations are. Many use an elaborate network of freezers and specialised trucks and aircraft to move temperature-sensitive materials such as blood, stem cells and tissue around the world without compromising their efficacy. Its a delicate process, because a product can go from vital to useless within minutes of being removed from cold storage.

Potential investors are constantly calling Stirling Ultracold, whose freezer equipment is powering UPS freezer farms in Louisville, Kentucky, and the Netherlands, where vaccines will be stored. Theres not a day that goes by that an inquiry doesnt come in, said Dusty Tenney, Stirlings chief executive, who is running his Athens, Ohio, production lines around the clock.

Demand for Stirlings freezer engines the core component of its upright, under-the-counter and portable freezers has soared, and the estimated waiting time for new orders is six to eight weeks, the company said. On December 8, after multiple prospective investors studied the companys financial metrics in a due diligence process, Stirling received a capital injection of an undisclosed amount that it plans to use to buy new equipment and expand production.

In October, Blackstone, the private equity giant, invested $275 million in Cryoport, a Nashville, Tennessee company that specializes in shipping sensitive medical materials at freezing temperatures. Investors have also been bullish on Ember, the beverage-heating company that has developed a refrigerated medical shipping box with built-in GPS and already counts two Jonas Brothers and Brooklyn Nets forward Kevin Durant as shareholders.

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PCI Pharma recently changed ownership. The new investors, private-equity firm Kohlberg & Co. and Abu Dhabi, United Arab Emirates, sovereign-wealth fund Mubadala Investment Co., viewed the companys expertise in transporting pharmaceuticals globally during the pandemic as a potential benefit.

Cold-chain investors said they were drawn to the area well before the pandemic because of the boom in biologic drugs, which require blood, tissue and other vital materials to be transported at low temperatures. For now, though, the rush to develop and distribute Covid-19 vaccines has amped up investors enthusiasm.

In addition to Pfizer and Moderna, AstraZeneca, Johnson & Johnson and others are also developing vaccines that will require cold storage. Therefore, cold-chain infrastructure, which can be limited in rural or far-flung areas like southeastern Indiana and Hawaii, will be essential.

Shares of Cryoport, which ships biologic material at cryogenic temperatures a level of freezing, usually around minus 150 Celsius, at which cells and other living materials enter a quiescent state are up more than 180% this year. Already, the company has transported temperature-sensitive materials involved in 26 different Covid vaccines and treatments and has a long-term partnership with McKesson, a distributor of medical supplies that has been tapped by the US government to manage domestic vaccine distribution.

Jerrell Shelton, Cryoports chief executive, said he expected the company to be involved in the global distribution of the vaccine, but the details had not yet been determined. This is a massive, massive effort, and its going to strain the temperature-control supply chain throughout the world, he said.

Ram M. Jagannath, a senior managing director at Blackstone who oversees the firms investment in Cryoport, said that the cell and gene-based therapies market in which the company operates is likely to grow at an annualised rate of 50% for the next five years. The current pandemic has only served to increase interest and investment in these potentially lifesaving therapies, Jagannath said. We invested in this for the long run.

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Then there are companies like Ember, which is hoping to parlay its temperature-control technology currently used in a smart mug that keeps beverages at the users preferred drinking temperature into a shipping container for the Covid vaccine. Several years ago, Ember built a portable refrigerator for Mayo Clinic physicians trying to deliver vaccines to places where dry ice and cooling facilities were scarce.

We tested it, and we got huge positive feedback, said Clay Alexander, Embers chief executive.

That led to the creation of Embers cold box, which can ship medical products at standard refrigeration temperatures and generate its own electronic return labels on arrival a product it plans to take wider next year through a commercial partnership it signed recently. Investors in Ember are hoping that the technology will also come in handy as delivery of Covid vaccines becomes more widespread.

Much of the cold-chain infrastructure for pharmaceuticals was already in place in 2014, when veteran health care investor Matthew J. Jennings attended a gathering of the cold-chain industrys trade association in Chicago.

I was surprised at the size of the industry and the number of exhibitors searching for growth, said Jennings, an operating partner at Kohlberg who is now chairman of PCI Pharma. Growth, he said, has accelerated since then, and will likely benefit again as a result of Covid.

On November 20, a shipment of a Covid vaccine PCI Pharmas Haffar wouldnt say which one arrived at the companys headquarters as part of a dry run, escorted by armed US marshals.

The vials containing the vaccine were stored in a PCI refrigerator set between 2 and 8 degrees Celsius and monitored constantly. Once ready for packaging, the vials were removed from storage and brought to a machine where they were labelled and boxed before being returned to cold storage.

Haffar gave a tour recently of the companys Philadelphia building. Inside a walk-in cooler and wearing a long-sleeved gown and hairnet, he motioned to the surrounding shelves. They contained rows and rows of products that PCI packages, including drugs that treat Crohns disease and syringes that inject medicines directly into the eye.

The cold chain has been around forever, he said. The vaccine just made the sheer size of it bigger.

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The unsexy side of Covid-19 vaccines gets Wall Streets attention - Deccan Herald

MUSC Hollings Cancer Center researchers identified that blocking an alternative energy pathway for T-cells after hematopoietic stem cell transplant helps reduce graft-versus-host disease (GVHD) in an animal model of leukemia.

Xue-Zhong Yu, M.D., who also is associate director of Basic Science at Hollings, and collaborators at the Indiana University School of Medicine discovered that donor T-cells must have the key enzyme lysosomal acid lipase in order to induce GVHD.

The Yu laboratory focuses on understanding the biological balance between GVHD and graft-versus-leukemia effect. Hematopoietic stem cell transplantation is used as a treatment option for some leukemia patients. T-cells in stem cell grafts from a donor are given to a leukemia patient in order to kill the cancer and reboot the patient's immune system. GVHD is a big clinical challenge because the donor T-cells, which come from the bone marrow, can attack the patient's organs. Anywhere from 30% to 70% of patients develop acute GVHD after allogeneic bone marrow transplant and 15% die.

"When we deal with hematopoietic cell transplant, it is an important balance - blocking GVHD while still allowing T-cells to do their job and control the cancer," Yu said.

Each cell in our body has its own metabolic process. Cells convert the food that is eaten into energy in order to perform their intended functions. However, cellular metabolism is often altered in various diseases. Yu researches T-cell metabolism in order to understand the balance between graft-versus-host and graft-versus-leukemia responses.

Most cells in our body require oxygen to create energy efficiently. However, this research focused on lipid, or fat, metabolism. T-cells have special metabolic processes: Sometimes they multiply so rapidly that they need an extra source of energy from free fatty acids.

Lysosomal acid lipase is an enzyme that breaks the large lipids and cholesterol into individual free fatty acid building blocks. If that enzyme is missing, there are not enough free fatty acids for energy production. This changes the T-cell metabolism, which in turn changes T-cell function.

Clinically, broad spectrum immunosuppression drugs (steroids and rapamycin) are still used as the first line of care in patients with severe GVHD. However, Yu and collaborators hypothesized that changing T-cell metabolism could reduce GVHD after hematopoietic stem cell transplantation.

"We know that the gut is the primary organ affected by GVHD. Since the gut has less oxygen, the T-cells rely on free fatty acids and must use lysosomal acid lipase. We thought if we could remove or block the activity of that, we could reduce GVHD in the gut."

The Yu Laboratory collaborated with the Indiana University School of Medicine and used a lysosomal acid lipase-deficient mouse model. T-cells lacking lysosomal acid lipase were given to mice with leukemia. As a control, T-cells with lysosomal acid lipase from normal mice were given to another group of leukemia mice. Strikingly, the mice that received the T-cells without lysosomal acid lipase did not get severe GVHD. Additionally, the T-cells from the donor lysosomal acid lipase-deficient bone marrow still killed the leukemia cells.

To increase the clinical translational potential of the work, orlistat, the FDA-approved lysosomal acid lipase inhibitor was also tested in the leukemia model. Mice with leukemia were treated with orlistat every other day after receiving bone marrow from normal mouse donors. Similar to the first experiment with the lysosomal acid lipase-deficient bone marrow, blocking the activity of lysosomal acid lipase with orlistat greatly reduced GVHD while the graft-versus-leukemia effect was preserved.

Additionally, the researchers discovered that inhibiting the lysosomal acid lipase enzyme with orlistat reduced the number of pathogenic T-cells and increased the number of regulatory T-cells. The pathogenic T-cells are the ones that cause GVHD. Regulatory T-cells are one of the "braking mechanisms" of the immune system. They help to reduce the activity of the pathogenic T-cells and prevent GVHD damage.

Therefore, blocking lysosomal acid lipase activity with orlistat preferentially stopped the donor T-cells from damaging the gut but allowed the T-cells to function during circulation and kill the leukemia cells.

The researchers' future plan is to look deeper at the biological mechanisms. For example, it is not clear how the loss or inhibition of lysosomal acid lipase affects the other metabolites in T-cells. To move this finding closer to the clinic, Yu explained that human cells can be used in a special mouse model that recreates the human immune environment.

"Looking at the immune cells in the gut was technically challenging. However, the results were exciting because our hypothesis was validated. These results encourage us to continue studying this in order to provide better treatment options to patients."

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Blocking energy pathway reduces GVHD while retaining anti-cancer effects of T-cells - Science Codex