Category Archives: Cell Medicine

UC San Francisco researchers have identified cells unique features within the developing human brain, using the latest technologies for analyzing gene activity in individual cells, and have demonstrated that large-scale cell surveys can be done much more efficiently and cheaply than was previously thought possible.

Arnold Kriegstein, MD, PhD

We have identified novel molecular features in diverse cell types using a new strategy of analyzing hundreds of cells individually, said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. We expect to use this approach to help us better understand how the complexity of the human cortex arises from cells that are spun off through cell division from stem cells in the germinal region of the brain.

The research team used technology focused on a microfluidic device in which individual cells are captured and flow into nano-scale chambers, where they efficiently and accurately undergo the chemical reactions needed for DNA sequencing. The research showed that the number of reading steps needed to identify and spell out unique sequences and to successfully identify cell types is 100 times fewer than had previously been assumed. The technology, developed by Fluidigm Corporation, can be used to individually process 96 cells simultaneously.

The routine capture of single cells and accurate sampling of their molecular features now is possible, said Alex Pollen, PhD, who along with fellow Kriegstein-lab postdoctoral fellow Tomasz Nowakowski, PhD, conducted the key experiments, in which they analyzed the activation of genes in 301 cells from across the developing human brain. Their results were published online August 3 in Nature Biotechnology.

Kriegstein said the identification of hundreds of novel biomarkers for diverse cell types will improve scientists understanding of the emergence of specialized neuronal subtypes. Ultimately, the combination of this new method of focusing on gene activity in single cells with other single-cell techniques involving microscopic imaging is likely to reveal the origins of developmental disorders of the brain, he added.

The process could shed light on several brain disorders, including lissencephaly, in which the folds in the brains cortex fail to develop, as well as maladies diagnosed later in development, such as autism and schizophrenia, Kriegstein said.

According to the Nature Biotechnology study co-authors, this strategy of analyzing molecules in single cells is likely to find favor not only among researchers who explore how specialized cells arise at specific times and locations within the developing organism, but also among those who monitor cell characteristics in stem cells engineered for tissue replacement, and those who probe the diversity of cells within tumors to identify those responsible for survival and spread of cancerous cells.

No matter how pure, in any unprocessed biological sample there are a variety of cells representing various tissue types. Researchers have been sequencing the combined genetic material within these samples. To study which genes are active and which are dormant, they use the brute repetition of sequencing steps to capture an adequate number of messenger RNA sequences, which are transcribed from switched-on genes. However, it is difficult to conclude from mixed tissue samples which genes are expressed by particular cell types.

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Single-Cell Analysis Holds Promise for Stem Cell and Cancer Research

PUBLIC RELEASE DATE:

31-Jul-2014

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research

Advances in stem cell research will provide enormous opportunities for both biological and future clinical applications. Basically, stem cells could replicate any other cells in the body, offering immense hope of curing Alzheimer's disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. The potential for profit is staggering. Prof. Jinhui Chen from Indiana University in USA considered that this field of research still faces myriad biological, ethical, legal, political, and financial challenges. The eventual resolution of these conflicts will determine the success of the research and potentially the face of medicine in the future. The relevant study has been published in the Neural Regeneration Research (Vol. 9, No. 7, 2014).

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Article: " A brief review of recent advances in stem cell biology " by Jinhui Chen1, Libing Zhou2, Su-yue Pan3 (1 Stark Neuroscience Research Institute and Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; 2 Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, Guangdong Province, China; 3 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China)

Chen JH, Zhou LB, Pan SY. A brief review of recent advances in stem cell biology. Neural Regen Res.2014;9(7):684-687.

Contact: Meng Zhao eic@nrren.org 86-138-049-98773 Neural Regeneration Research http://www.nrronline.org/

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

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Recent advances in stem cell biology

By Amy Norton HealthDay Reporter

WEDNESDAY, July 30, 2014 (HealthDay News) -- Babies born with so-called "bubble boy" disease can often be cured with a stem cell transplant, regardless of the donor -- but early treatment is critical, a new study finds.

Severe combined immunodeficiency (SCID), as the condition is medically known, actually refers to a group of rare genetic disorders that all but eliminate the immune system. That leaves children at high risk of severe infections.

The term "bubble boy" became popular after a Texas boy with SCID lived in a plastic bubble to ward off infections. The boy, David Vetter, died in 1984 at the age of 12, after an unsuccessful bone marrow transplant -- an attempt to give him a functioning immune system.

Today, children with SCID have a high chance of survival if they receive an early stem cell transplant, researchers report in the July 31 issue of the New England Journal of Medicine.

In the best-case scenario, a child would get stem cells -- the blood-forming cells within bone marrow -- from a sibling who is a perfect match for certain immune-system genes.

But that's not always an option, partly because kids with SCID are often their parents' first child, said Dr. John Cunningham, director of hematopoietic stem cell transplantation at the University of Chicago Comer Children's Hospital. He was not involved in the study.

In those cases, doctors typically turn to a parent -- who is usually a "half" match, but whose stem cells can be purified to improve the odds of success. Sometimes, stem cells from an unrelated, genetically matched donor can be used.

The good news: Regardless of the donor, children with SCID can frequently be cured, according to the new findings. But early detection and treatment is vital.

"These findings show that if you do these transplants early -- before [the age of] 3.5 months, in a child without infection -- the results are really quite comparable to what you have with a matched sibling," said lead researcher Dr. Richard O'Reilly, chief of the pediatric bone marrow transplant service at Memorial Sloan-Kettering Cancer Center in New York City.

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Early Stem Cell Transplant Vital in 'Bubble Boy' Disease

Boston, MA (PRWEB) July 31, 2014

Bostons Adult Stem Cell Technology Center, LLC (ASCTC) finds itself flush with innovative adult stem cell biotechnologies. Currently the company holds seven recently issued patents and has three additional patent applications currently under examination by the U.S. Patent and Trademarks Office.

The patented inventions address two of the most vexing problems in adult stem cell biology research and regenerative medicine. Adult stem cells are difficult to identify; and they have been difficult to multiply to sufficient numbers to support regenerative medicine applications.

ASCTC has addressed the identity problem by developing patented biomarkers that are found exclusively on adult stem cells. The biomarkers are based on ASCTCs expertise in defining properties of adult stem cells that are not shared by any other normal cell types in the body. The patented biomarkers also identify some types of cancer stem cells. Therefore, they have applications in both stem cell medicine and cancer medicine.

ASCTCa success in developing procedures for producing adult stem cells in large numbers is due to the companys expertise in adult stem cell growth control. ASCTCs technology uses natural compounds found in the body to instruct adult stem cells to multiply in a controlled manner as during normal body growth.

The companys patented method for controlling adult stem cells to multiply without losing their stem cell properties has applications for many different types of adult stem cells. ASCTCs approved patents demonstrate the application of the method for production of human liver stem cells, hair follicle stem cells, and human pancreatic stem cells; but the technology has general application to adult stem cells found in many other types of organs and tissues.

In addition to the main focus on adult stem cell technologies, ASCTCs most recently issued patent applies its cell multiplication methods to produce induced pluripotent stem cells (iPSCs) without transferring exogenous genes. This gene-free single agent method should offer significant value to the many mushrooming companies that supply iPSCs and iPSC production reagents.

As a small start-up, ASCTC is employing a social media marketing strategy. In the past week, the company has launched patent licensing ads on LinkedIn, Vocus, and Facebook, as well increased its advertising references within its recently established Twitter presence.

It would be a shame for these technologies to lie dormant, just because our hands are full with other projects at the moment. James Sherley, director of ASCTC, relates that the companys two main business efforts require only a fraction of its available intellectual property. ASCTC is currently focused on bringing laboratory-scale production of human liver stem cells to manufacturing scales and developing a computer simulation assay for preclinical detection of drug candidates with intolerable toxicity due to adverse effects on adult stem cells.

Sherley adds, We already have a few companies that have expressed interest in licensing. But we could do a lot better at reaching others whose development efforts would benefit from ASCTCs unique technologies. Love to hear from ViaCyte!

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The Adult Stem Cell Technology Center, LLC Launches A Marketing Campaign To License Adult Stem Cell Biotechnologies

"Bubble boy" David Vetter lived in a protective environment designed by NASA engineers. He died of complications after receiving a bone marrow transplant in 1984, at the age of 12. Baylor College of Medicine Photo Archives

Babies born with so-called "bubble boy" disease can often be cured with a stem cell transplant, regardless of the donor -- but early treatment is critical, a new study finds.

Severe combined immunodeficiency (SCID), as the condition is medically known, actually refers to a group of rare genetic disorders that all but eliminate the immune system. That leaves children at high risk of severe infections.

The term "bubble boy" became popular after a Texas boy with SCID lived in a plastic bubble to ward off infections. The boy, David Vetter, died in 1984 at the age of 12, after an unsuccessful bone marrow transplant -- an attempt to give him a functioning immune system.

15 Photos

Immune disorder forced David Vetter to live in bubble - but breakthroughs from his story now enable similar kids to live free

In the best-case scenario, a child would get stem cells -- the blood-forming cells within bone marrow -- from a sibling who is a perfect match for certain immune-system genes.

But that's not always an option, partly because kids with SCID are often their parents' first child, said Dr. John Cunningham, director of hematopoietic stem cell transplantation at the University of Chicago Comer Children's Hospital. He was not involved in the study.

In those cases, doctors typically turn to a parent -- who is usually a "half" match, but whose stem cells can be purified to improve the odds of success. Sometimes, stem cells from an unrelated, genetically matched donor can be used.

The good news: Regardless of the donor, children with SCID can frequently be cured, according to the new findings. But early detection and treatment is vital.

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Early stem cell transplant may cure "bubble boy" disease

Autism Protocol

Current investigative therapies for autism attempt to reverse these abnormalities through administration of antibiotics, antiinflammatory agents, and hyperbaric oxygen. Unfortunately, none of these approaches address the root causes of oxygen deprivation and intestinal inflammation.

Mesenchymal stem cells can regulate the immune system. It is thought that they may help to reverse inflammatory conditions and is currently in the final stages of clinical trials in the US for Crohns disease, a condition resembling the gut inflammation in autistic children.

Through administration of mesenchymal stem cells, we have observed improvement in subjects to whom weve administered stem cells at our facilities. The biological basis for our scientists appears in a peer-reviewed publication Journal of Translational Medicine: Stem Cell Therapy for Autism.

The adult stem cells used in the autism clinical investigation at the Stem Cell Institute come from human umbilical cord tissue (allogeneic mesenchymal). These stem cells are recovered from donated umbilical cords. Before they are approved for use, all umbilical cord-derived stem cells are screened for viruses and bacteria to International Blood Bank Standards. In some cases, we also utilize stem cells harvested from the subjects own bone marrow. Umbilical cord-derived stem cells are ideal for the autism protocol because they allow our physicians to administer uniform doses and they do not require any stem cell collection from the subject, which for autistic children and their parents, can be an arduous process. Because they are collected right after (normal) birth, umbilical cord-derived cells are much more potent than their older counterparts like bone marrow-derived cells for instance. Cord tissue-derived mesenchymal stem cells pose no rejection risk because the body does not recognize them as foreign.

Because HUCT stem cells are less mature than other cells, the bodys immune system is unable to recognize them as foreign and therefore they are not rejected. Weve performed thousands of procedures with umbilical cord stem cells and there has never been a single instance of rejection. HUCT stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the bone marrow and therefore, they are considered to be more potent.

The umbilical cord-derived stem cells are administered intravenously by a licensed physician.

Below is an example of a typical autism schedule. Our investigational clinical protocol for autism (www.clinicaltrials.gov NCT02192749) has been approved by the National Institutional Review Board for Clinical Protocols.

Proper follow-up is an essential part of the autism clinical investigation process. Our primary goal is to ensure that your child is progressing safely. Regular follow-up also enables us to evaluate efficacy and improve our autism clinical protocols based on observed outcomes.

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Stem Cell Therapy for Autism || Treatment Information ...

The California Institute for Regenerative Medicine has continued in damage-control mode since the state agencys former president, Alan Trounson, joined the board of directors at StemCells Inc. this month, just seven days after leaving the agency.

Newark-based StemCells has been awarded nearly $20 million in CIRM funding, as part of a long relationship that, in the wake of Trounson's departure, has raised concern about potential conflict of interest.

The agency's new president, C. Randal Mills, said he was taking a strong stand on personal ethics, signing an agreement not to accept a job with any company funded by CIRM for at least one year after leaving his position at the state agency.

"We take even the appearance of conflicts of interest very seriously," Mills said in a statement this month.

But a scientist whose grant proposal was turned down even though it received a higher rating than the StemCells proposal called the relationship between the state agency and the company interesting.

In my opinion, Mr. Trounson and the CIRM staff were clearly antagonistic to us and strongly supportive of StemCells, Lon S. Schneider, a scientist at USCs Keck School of Medicine, told the California Stem Cell Report ,a blog that follows news related to the stem cell agency.

And Times columnist Michael Hiltzik pointed out that the agency has hired its own law firm to conduct the investigation, rather than a completely independent party.

The unanswered question burning a hole through CIRM's credibility is whether StemCells Inc. got its money because its research was promising, or because it knew the right people, Hiltzik wrote.

The stem cell agency has also voted to cut $5 million from a $70-million effort to create a series of statewide stem cell clinics, according to the California Stem Cell Report. And even though the board has 29 members, only eight could vote because of conflicts of interest among the others, according to the report.

Following a thorough review it is my opinion that the $70-million price tag is not clearly justified in terms of the benefits it will deliver to the people of California, Mills wrote in a memo to the agency's board.

Original post:
California stem cell agency head takes stand on 'personal ethics'

Professor John Rasko on SBS Insight
Royal Prince Alfred Hospital #39;s Director of Cell and Molecular Therapies, Professor John Rasko, was invited as a guest on SBS Insight #39;s special on stem cell medicine.

By: SydneyLHD

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Professor John Rasko on SBS Insight - Video

There's no good time for a public agency to be embroiled in a conflict-of-interest scandal, but this is an especially delicate time for California's stem cell agency.

The California Institute for Regenerative Medicine, as the program is known formally, is on track to finish doling out its $3 billion in funding from the state's voters as soon as 2017. Its original sponsor, Northern California real estate developer Robert Klein II, has been quoted talking about another $5-billion infusion, perhaps via the 2016 ballot.

Any such effort will refocus attention on the program board's inherent conflicts of interest, which were baked in by the terms of Proposition 71, Klein's 2004 ballot initiative that created CIRM and funded it through a bond issue. The prestigious Institute of Medicine in a 2012 report found these conflicts to lead to questions about "the integrity and independence of some of CIRM's decisions."

And now here comes another case. This one involves CIRM former President Alan Trounson, an Australian biologist who left the agency on June 30 and joined the board of one of its highest-profile financial partners a mere seven days later. Trounson's new employer, Stem Cells Inc., is the recipient of a nearly $20-million loan for Alzheimer's research.

CIRM says Trounson's quick move to Stem Cells Inc., where he'll receive a stipend of at least $90,000 a year, is legally "permissible." But officials there acknowledge they were blindsided; the agency learned about Trounson's new position from the company's press release.

Afterward, CIRM rushed out a statement acknowledging that Trounson's appointment to the board of a CIRM loan recipient "creates a serious risk of a conflict of interest." The agency says it will place the relationship between CIRM and the company under "a full review." Administrators reminded Trounson, board members and agency staff that state law bars him from communicating with them on any administrative matter involving Stem Cells Inc. The company declined to comment.

The relationship already reeked of cronyism. As we reported in 2012, the Newark, Calif.-based firm's co-founder, Irving Weissman, director of Stanford University's Institute for Stem Cell Biology and Regenerative Medicine, had been one of the most prominent and outspoken supporters of Proposition 71.

He's also a leading recipient of CIRM funding, listed as the principal investigator on four Stanford grants totaling nearly $35 million. CIRM contributed $43.6 million toward the construction of his institute's $200-million research building at the Stanford campus. Weissman and his wife, Ann Tsukamoto, owned nearly 380,000 shares of the firm as of last April, according to a corporate disclosure. Tsukamoto is one of the company's top executives; Weissman is a board member.

Trounson's move comes as CIRM must begin looking to the future, but any discussions about extending the agency's life span will have to address the flaws created by Proposition 71. Among them is the program's very structure, and even its scientific goals.

Klein's ballot proposition exempts CIRM from virtually any oversight or accountability. Each of the 29 governing board members has to be associated with a California public or private research institution or company, or an advocacy group for patients of one disease or another. The qualifications for board chairman are so specific they initially yielded a single credible candidate: Bob Klein.

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Conflicts of interest pervasive on California stem cell board

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Newswise Researchers at the National Institutes of Health have developed a technique that will speed up the production of stem-cell derived tissues. The method simultaneously measures the expression of multiple genes, allowing scientists to quickly characterize cells according to their function and stage of development. The technique will help the researchers in their efforts to use patients skin cells to regenerate retinal pigment epithelium (RPE)a tissue in the back of the eye that is affected in several blinding eye diseases. It will also help the scientists search for drugs for personalized treatments.

Progress in stem cell-based therapies has been limited by our capacity to authenticate cells and tissues, said Kapil Bharti, Ph.D., a Stadtman Investigator in the Unit on Ocular and Stem Cell Translational Research at the National Eye Institute (NEI), a part of NIH. This assay expands that capacity and streamlines the process.

The assay was described in a recent issue of Stem Cells Translational Medicine.

The RPE is a single layer of cells that lies adjacent to the retina, where the light-sensitive photoreceptors commonly called rods and cones are located. The RPE supports photoreceptor function. Several diseases cause the RPE to break down, which in turn leads to the loss of photoreceptors and vision.

The stem cells Dr. Bharti is using to make RPE are induced pluripotent (iPS) stem cells, which are produced by reverting mature cells to an immature state, akin to embryonic stem cells. iPS cells can be derived from a patients skin or blood cells, coaxed into other cell types (such as neurons or muscle), and in theory, re-implanted without causing immune rejection.

To verify the identity of RPE made from iPS cells, scientists use microscopy to ensure the tissue looks like RPE and physiological assays to ensure the tissue behaves like RPE. They also use a technique called quantitative RT-PCR to measure the expression of genes that indicate ongoing cell development and function. For example, expression of the gene SOX2 is much higher in iPS cells than mature RPE.

But quantitative RT-PCR only permits the simultaneous measurement of a few genes per sample. Dr. Bharti teamed up with Marc Ferrer, Ph.D., of NIHs National Center for Advancing Translational Sciences (NCATS) to develop a multiplex assaya method for simultaneously measuring multiple genes per RPE sample in a highly automated fashion. The assay is based on a commercially available platform from the biotech company Affymetrix. In the assay, tiny snippets of DNA tethered to beads are used to capture RNA moleculescreated when genes are expressed by cells in the RPE sample. Once captured, the RNA from distinct genes is labeled with a fluorescent tag.

Starting with cells from a skin biopsy, the researchers generated iPS-derived RPE and then measured the expression of eight genes that are markers of development, function, and disease. They measured RNA levels of each gene one at a time using quantitative RT-PCR and then all genes simultaneously using the multiplex assay. When compared, the results correlated.

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Gene Profiling Technique to Accelerate Stem Cell Therapies for Eye Diseases