Category Archives: Stem Cells

Jan. 2, 2014 Biologists at UC San Diego have discovered an effective strategy that could prevent the human immune system from rejecting the grafts derived from human embryonic stem cells, a major problem now limiting the development of human stem cell therapies. Their discovery may also provide scientists with a better understanding of how tumors evade the human immune system when they spread throughout the body.

The achievement, published in a paper in this week's early online edition of the journal Cell Stem Cell by a collaboration that included scientists from China, was enabled by the development of "humanized" laboratory mice that contained a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived from human embryonic stem cells.

Because human embryonic stem cells are different from our own body's cells, or "allogenic," a normally functioning human immune system will attack these foreign cells. One way to reduce the body's "allogenic immune response" is to suppress the immune system with immunosuppressant drugs.

"For organ transplantation to save patients with terminal diseases that has been quite successful," says Yang Xu, a professor of biology who headed the team of researchers that included Ananda Goldrath, an associate biology professor at UC San Diego. "But for stem cell therapies, the long term use of toxic immunosuppressant drugs for patients who are being treated for chronic diseases like Parkinson's disease or diabetes pose serious health problems."

Researchers had long been searching for a human immunity relevant model that would allow them to develop strategies to implant allogenic cells derived from embryonic stem cells safely. "The problem is that we only had data from mouse immune system and those are not usually translatable in humans, because human and mouse immune systems are quite different," explains Xu. "So what we decided to do was to optimize the humanized mouse that carries a functional human immune system."

To do that, the biologists took immune deficient laboratory mice and grafted into their bodies human fetal thymus tissues and hematopoietic stem cells derived from fetal liver of the same human donor. "That reconstituted in these mice a normally functioning human immune system that effectively rejects cells derived human embryonic stem cells," says Xu. With these "humanized" mouse models, the biologists then tested a variety of immune suppressing molecules alone or in combination and discovered one combination that worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.

That combination was CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis that suppresses T-cells responsible for immune rejection, and a protein called PD-L1 known to be important for inducing immune tolerance in tumors. The researchers discovered that the combination of these two molecules allowed the allogeneic cells to survive in humanized mice without triggering an immune rejection.

"If we express both molecules in cells derived from human embryonic cells, we can protect these cells from the allogenic immune rejection," says Xu. "If you have only one such molecule expressed, there is absolutely no impact. We still don't know exactly how these pathways work together to suppress immune rejection, but now we've got an ideal system to study this."

He and his team of researchers also believe their discovery and the development of their humanized mouse models may offer the much needed tools to develop ways to activate immune response to tumors, because these molecules are known to be important in allowing tumors to evade the human immune system.

"You're dealing with the same exact pathways that protect tumors from our immune system," says Xu. "If we can develop strategies to disrupt or silence these pathways in tumors, we might be able to activate immunity to tumors. The humanized mouse system is really a powerful model with which to study human tumor immunity."

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Solution found to problem limiting development of human stem cell therapies

PUBLIC RELEASE DATE:

2-Jan-2014

Contact: Kim McDonald kmcdonald@ucsd.edu 858-534-7572 University of California - San Diego

Biologists at UC San Diego have discovered an effective strategy that could prevent the human immune system from rejecting the grafts derived from human embryonic stem cells, a major problem now limiting the development of human stem cell therapies. Their discovery may also provide scientists with a better understanding of how tumors evade the human immune system when they spread throughout the body.

The achievement, published in a paper in this week's early online edition of the journal Cell Stem Cell by a collaboration that included scientists from China, was enabled by the development of "humanized" laboratory mice that contained a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived from human embryonic stem cells.

Because human embryonic stem cells are different from our own body's cells, or "allogenic," a normally functioning human immune system will attack these foreign cells. One way to reduce the body's "allogenic immune response" is to suppress the immune system with immunosuppressant drugs.

"For organ transplantation to save patients with terminal diseases that has been quite successful," says Yang Xu, a professor of biology who headed the team of researchers that included Ananda Goldrath, an associate biology professor at UC San Diego. "But for stem cell therapies, the long term use of toxic immunosuppressant drugs for patients who are being treated for chronic diseases like Parkinson's disease or diabetes pose serious health problems."

Researchers had long been searching for a human immunity relevant model that would allow them to develop strategies to implant allogenic cells derived from embryonic stem cells safely. "The problem is that we only had data from mouse immune system and those are not usually translatable in humans, because human and mouse immune systems are quite different," explains Xu. "So what we decided to do was to optimize the humanized mouse that carries a functional human immune system."

To do that, the biologists took immune deficient laboratory mice and grafted into their bodies human fetal thymus tissues and hematopoietic stem cells derived from fetal liver of the same human donor. "That reconstituted in these mice a normally functioning human immune system that effectively rejects cells derived human embryonic stem cells," says Xu. With these "humanized" mouse models, the biologists then tested a variety of immune suppressing molecules alone or in combination and discovered one combination that worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.

That combination was CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis that suppresses T-cells responsible for immune rejection, and a protein called PD-L1 known to be important for inducing immune tolerance in tumors. The researchers discovered that the combination of these two molecules allowed the allogeneic cells to survive in humanized mice without triggering an immune rejection.

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Biologists discover solution to problem limiting development of human stem cell therapies

Dec 31, 2013 by John Steeno

(Phys.org) A team of engineers at the University of Wisconsin-Madison has created a process that may revolutionize stem cell research. The process, outlined in a paper published in Stem Cells on December 19, 2013, will improve the state of the art in the creation of synthetic neural stem cells for use in central nervous system research.

Human pluripotent stem cells have been used to reproduce nervous-system cells for use in the study and treatment of spinal cord injuries and of diseases such as Parkinson's and Huntington's. Currently, most stem cells used in research have been cultured on mouse embryonic fibroblasts (MEFs), which require a high level of expertise to prepare. The expertise required has made scalability a problem, as there can be slight differences in the cells used from laboratory to laboratory, and the cells maintained on MEFs are also undesirable for clinical applications.

Removing the high level of required skilland thereby increasing the translatability of stem cell technologyis one of the main reasons why Randolph Ashton, a UW-Madison assistant professor of biomedical engineering and co-author of the paper, wanted to create a new protocol.

Rather than culturing stem cells on MEFs, the new process uses two simple chemical cocktails to accomplish the same task. The first mixture, developed by John D. MacArthur Professor of Medicine James Thomson in the Morgridge Institute for Research, is used to maintain the stem cells in the absence of MEFs. The second cocktail allows researchers to push the stem cells toward a neural fate with very high efficiency.

These chemical mixtures help to ensure the consistency of the entire process and give researchers a better understanding of what is driving the differentiation of the cells. "Once you remove some of the confounding factors, you have better control and more freedom and flexibility in terms of pushing the neural stem cells into what you want them to become," says Ashton.

Streamlining the process also removes some of the ambiguities that were inserted with MEFs. And Ashton hopes the straightforward protocol will enable other labs to engage in more complex tissue engineering. "Ours is the simplest, fastest and most efficient way to generate these types of cells," he says.

Ethan Lippmann, a postdoctoral fellow at the Wisconsin Institute for Discovery and co-author on the paper, says the major impact of this new process on other labs will be two-fold. "It's incredibly easy and simplified, and you can buy everything 'off the shelf,' so to speak," he says. "This should allow other researchers who are not stem cell experts to adapt this protocol to their own labs. We also want people to look at the things we do, as we generate more specialized neural cell types using this protocol, and feel comfortable that they can be translated to a clinic."

Explore further: HEXIM1 regulatory protein induces human pluripotent stem cells to adopt more specialized cell fate

A lot of optimism and promise surrounds the use of human pluripotent stem cells (hPSCs)for applications in regenerative medicine and drug discovery. However, technical challenges still hamper the culturing ...

Read more here:
A paradigm-shifting step in stem cell research

The University of Queensland mini-kidney

Instead of having to wait for one of the limited number of available donor kidneys, patients in need of a transplant may eventually be able to have a new kidney custom-grown for them. That possibility recently took one step closer to reality, as scientists at Australia's University of Queensland successfully grew a "mini-kidney" from stem cells.

The researchers created a proprietary new protocol, that prompts stem cells in a petri dish to self-organize into a miniature kidney. "During self-organization, different types of cells arrange themselves with respect to each other to create the complex structures that exist within an organ, in this case, the kidney," says project leader Prof. Melissa Little.

Stem cells, as many readers will already know, are essentially "blank slate" cells that are able to become any of a wide variety of specialized cells. Previous studies have coaxed them into becoming lung, retina and brain cells, among other types.

Little points out that while the work is indeed promising, human trials with full-size lab-grown kidneys are not likely to be happening anytime soon. In the meantime, however, the mini-kidneys could be used to test drug candidates without exposing human test subjects to harmful side effects.

A paper on the research was recently published in the journal Nature Cell Biology.

Earlier this year, scientists at the Massachusetts General Hospital Center for Regenerative Medicine created a functioning rat kidney. In their case, however, they did so by stripping the cells from an existing kidney, then "reseeding" the resulting collagen scaffold with endothelial cells.

Additionally, a team from Italys Mario Negri Institute for Pharmacological Research has created kidney-like organoids that perform the same functions as kidneys when implanted in rats.

Source: University of Queensland

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"Mini-kidney" grown from stem cells

PITTSBURGH (KDKA) Hayley Mogul, 13, and her 9-year-old sister, Bari, have rare genetic mutations that cant be cured.

But their conditions have improved during a two-month stay at the Childrens Institute in Squirrel Hill.

Their mother, Robyn Mogul, says she and her husband brought them here from their home of Chicago.

Haley could communicate, Robyn says. She could do some things herself, where Bari does not eat on her own. Shes eating baby food; she drinks out of a bottle.

Feeding specialist Natalie Chalmers says Bari is making progress.

She was on baby food only, she recalls. So weve been moving on to pureed table foods, and now were working on her variety.

Originally, the girls parents didnt know a place like this existed.

After Bari turned 5, the two sisters were taken to the National Institutes of Health in Bethesda, Md., for the first of several visits.

Doctors finally recommended the Childrens Institute of Pittsburgh.

To be able to come here and have this help has just been amazing, their mother says.

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Sisters’ Stem Cells Donated In Hopes Of Helping Other Children

MELBOURNE: Doctors may soon be able to draw new bone, skin and muscle on to patients, after scientists created a pen-like device that can apply human cells directly on to seriously injured people.

The device contains stem cells and growth factors and will give surgeons greater control over where the materials are deposited.

It will also reduce the time the patient is in surgery by delivering live cells and growth factors directly to the site of injury, accelerating the regeneration of functional bone and cartilage, scientists said.

The device developed at the University of Wollongong (UOW) will eliminate the need to harvest cartilage and grow it for weeks in a lab.

The Bio Pen works similar to 3D printing methods by delivering cell material inside a bio-polymer such as alginate, a seaweed extract, protected by a second, outer layer of gel material.

The two layers of gel are combined in the pen head as it is extruded onto the bone surface and the surgeon draws with the ink to fill in the damaged bone section.

A low powered ultra-violet light source is fixed to the device that solidifies the inks during dispensing, providing protection for the embedded cells while they are built up layer-by-layer to construct a 3D scaffold in the wound site.

Once the cells are drawn onto the surgery site they will multiply, become differentiated into nerve cells, muscle cells or bone cells and will eventually turn from individual cells into a thriving community of cells in the form of a functioning a tissue, such as nerves, or a muscle.

The device can also be seeded with growth factors or other drugs to assist regrowth and recovery, while the hand-held design allows for precision in theatre and ease of transportation.

The BioPen prototype was designed and built using the 3D printing equipment in the labs at Wollongong and was handed over to clinical partners at St Vincents Hospital Melbourne, led by Professor Peter Choong, who will work on optimising the cell material for use in clinical trials.

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New pen-like device to repair broken bone

Baishali Adak, Dec 26, 2013, DHNS :

Theoretically speaking, the concept of cord blood banking in India has been in circulation for quite some time. Educated and aware city-bred couples, who are expecting, are bound to have considered saving their newborns umbilical cord blood for regenerative and life-saving stem cells, in the past one or two decades. However, the last few years alone have seen a new vigour and assertiveness in the cord blood banking industry in India. Not just have new cord blood banks opened up (mainly branches of existing international ones) but they have also brought some innovative and aggressive marketing strategies with themselves.

Doctors say that now agents of these banks surround unsuspecting couples coming for prenatal checkups and convince them to buy their packages. About a month back, a leading cord blood bank also launched a TV commercial, whereby an expecting woman promises her baby the gift of life (read stem cells for possible future medical use), making many couples wonder if they are depriving their child by not going for it.

What do the doctors recommend?

Dr Meenakshi Sauhta, senior consultant Obstetrics and Gynaecology, Max Hospital, explains, Firstly, one must understand what cord blood banking is and why it is done. The blood in the umbilical cord of a baby, which is usually thrown away as medical waste, is actually rich in primitive stem cells. Stem cells are master cells which can grow into any kind of tissue including bones and blood once re-introduced in the body in the event of a medical problem.

Through research in the past few years, stem cells have been found to be effective in treating no less than 80 conditions ranging from various cancers to genetic and autoimmune disorders. With new trials proving them life-saving even in metabolic, brain and heart-related problems, the horizon is expanding rapidly, making cord blood banking essential day by day.

In US and several European countries, both public and private cord blood banks have existed alongside since the late 90s. In the public cord blood banking system, you voluntarily donate your babys cord blood, which becomes an anonymous property, and can retrieve any matching cord blood sample if required, years later. This is for free.

In the private system, though, you pay anywhere between Rs 22,000 to 1 lakh to store the blood which can be retrieved only by you or with your permission. The contract is for 21 years initially and you then pay annually for the storage depending on market rate. At the moment, only private cord blood banks exist in India.

Dr Venkatesh Ponemone, director, Totipotent RX Centre for Cellular Medicine, Gurgaon, says, Public banks are certainly a better idea but in their absence in India, couples can go for the private banks as well. The beauty of stem cells is that they are a perfect match for the family of a donor as well. Parents, grandparents, siblings, cousins can all use the stem cells if they get a medical condition anytime in future.

Today, worldwide, he adds, Over 25,000 cord blood transfusions are taking place annually. The interesting part is that only about 250 of these are autologous (donor receiving his own blood). The rest are all allogeneic (unrelated donors) or family members of the original patron.

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Banking on stem cells

By Scott M. Lippman

Chemotherapies seek out cancer cells by targeting a fundamental characteristic of cancer cells: their rapid and frequent replication. But in doing so, these drugs can destroy healthy cells that also grow quickly. The result: adverse effects like hair loss and nausea.Worse, the benefits of chemotherapy are frequently short-lived. Seemingly beaten by chemotherapy, a cancer can suddenly return, spreading from its original site to other parts of the body with often catastrophic consequences. Ninety percent of cancer-related deaths are due to metastasis, and almost every cancer can be metastatic.

Why do cancers recur when therapeutic evidence suggests theyve been wiped out? The answer lies in a type of cancer cell with the powerful characteristic of normal stem cells the ability to self-renew or regenerate.

Sott M. Lippman, M.D.

Unlike normal stem cells, however, this ability in cancer stem cells does not turn off.

Cancer stem cells are a relatively new phenomenon to cancer science. Conclusive evidence of their existence was found only in 1994, though in the years since, extraordinary efforts have been made to better understand them in order to destroy them.

Its a daunting task. Cancer stem cells persist in small communities, often tucked away in the deep recesses of bone. They do not divide with dangerous abandon, which would make them easier targets of chemotherapy. In fact, they often lie dormant, essentially invisible until they begin again the process of self-renewal, differentiation and cancer relapse.

Toughest of all, they are very hard to kill, quickly developing resistance to existing drug therapies.

Nonetheless, progress is being made, some of it driven by researchers at UC San Diego Moores Cancer Center. Among them is Catriona Jamieson, M.D., Ph.D., an associate professor of medicine in the UC San Diego School of Medicine and director of Stem Cell Research at Moores Cancer Center.

Jamieson has devoted much of her career to deciphering the secrets of cancer stem cells and, more importantly, working to develop effective treatments to rid the body of them. She specializes in myeloproliferative neoplasms (MPNs) and leukemia.

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FRONTLINE CANCER: Working to eliminate the cancer stem cells that sustain disease

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Highlights Investigators have discovered a cocktail of chemicals which, when added to stem cells in a precise order, turns on genes found in kidney cells in the same order that they turn on during embryonic kidney development. The kidney cells continued to behave like kidney cells when transplanted into adult or embryonic mouse kidneys.

Newswise Washington, DC (December 19, 2013) Researchers have successfully coaxed stem cells to become kidney tubular cells, a significant advance toward one day using regenerative medicine, rather than dialysis and transplantation, to treat kidney failure. The findings are published in the Journal of the American Society of Nephrology (JASN).

Chronic kidney disease is a major global public health problem, and when patients progress to kidney failure, their treatment options are limited to dialysis and kidney transplantation. Regenerative medicinewhich involves rebuilding or repairing tissues and organsmay offer a promising alternative.

Albert Lam, MD, Benjamin Freedman, PhD, Ryuji Morizane, MD, PhD (Brigham and Womens Hospital), and their colleagues have been working for the past five years to develop strategies to coax human pluripotent stem cellsparticularly human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cellinto kidney cells for the purposes of kidney regeneration.

Our goal was to develop a simple, efficient, and reproducible method of differentiating human pluripotent stem cells into cells of the intermediate mesoderm, the earliest tissue in the developing embryo that is fated to give rise to the kidneys, said Dr. Lam. He noted that these cells would be the starting blocks for deriving more specific kidney cells.

The researchers discovered a cocktail of chemicals which, when added to stem cells in a precise order, causes them to turn off genes found in ES cells and turn on genes found in kidney cells, in the same order that they turn on during embryonic kidney development. The investigators were able to differentiate both human ES cells and human iPS cells into cells expressing PAX2 and LHX1, two key markers of the intermediate mesoderm. The iPS cells were derived by transforming fibroblasts obtained from adult skin biopsies to pluripotent cells, making the techniques applicable to personalized approaches where the starting cells can be derived from skin cells of a patient. The differentiated cells expressed multiple genes expressed in intermediate mesoderm and could spontaneously give rise to tubular structures that expressed markers of mature kidney tubules. The researchers could then differentiate them further into cells expressing SIX2, SALL1, and WT1, important markers of the metanephric cap mesenchyme, a critical stage of kidney differentiation. In kidney development, the metanephric cap mesenchyme contains a population of progenitor cells that give rise to nearly all of the epithelial cells of the kidney.

The cells also continued to behave like kidney cells when transplanted into adult or embryonic mouse kidneys, giving hope that investigators might one day be able to create kidney tissues that could function in a patient and would be 100% immunocompatible.

We believe that the successful derivation of kidney progenitor cells or functional kidney cells from human pluripotent stem cells will have an enormous impact on a variety of clinical and translational applications, including kidney tissue bioengineering, renal assist devices to treat acute and chronic kidney injury, drug toxicity screening, screening for novel therapeutics, and human kidney disease modeling, said Dr. Lam.

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Researchers Generate Kidney Tubular Cells From Stem Cells

Democracy 3: United Kingdom - "Stem Cells Are Cool" [Part #5]
Elected Prime Minister after his party promised that they wouldn #39;t pass internet censorship, The ConflictNerd must now take the United Kingdom to new heights...

By: ConflictNerd

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Democracy 3: United Kingdom - "Stem Cells Are Cool" [Part #5] - Video