Category Archives: Stem Cells

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Previously, stem cells have been cultivated using animal proteins or by growing them from other human cells. Both methods come with associated problems. But, according to a study published in the journal Applied Materials & Interfaces, researchers have now identified a new method for cultivating stem cells.

Stem cells are a kind of cell that are able to divide or self-renew indefinitely. This allows the stem cell to generate into a range of different cell types for the organ that they originate from, or they may even be able to regenerate the whole organ.

Because of this, scientists are interested in using stem cells in a range of medical treatments, to replenish damaged tissue in the brain or skin, or as a treatment for diseases of the blood.

In adults, these stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin and liver. Adult stem cells only become "activated" and start dividing and generating new cells when their host tissue becomes damaged by disease or injury.

A more potent kind of stem cell is found in human embryos - this type has the unique ability to grow into any kind of cell in the human body. But using these cells in scientific research is controversial - and illegal in some countries - as harvesting them requires the destruction of a fertilized human egg (a "blastocyst") that has not had the chance to develop into a baby.

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Stem cells cultivated without using human or animal cells

CLEVELAND, OH Whod have ever thought something as unappealing as body fat could be useful much less lifesaving, right?

I think this will revolutionize medicine if it works, says Dr. Mark Foglietti of the Stem Cell Center of Ohio.

It turns out, fat is highly regenerative and rich in stem cells, Warren Buffett rich, having 2,500 times more stem cells than bone marrow.

And these are Mesenchymal stem cells. Mesenchymal meaning theyre able to change into whatever type of tissue theyre attracted to.

So doctors in Cleveland are trying an experimental procedure on Multiple Sclerosis patient Kym Sellers, She was saying Dad, if I could only just get the use of my hands. If I can just use my hands, I can comb my hair. I can feed myself.

Doctors liposuction fat from Sellers, take the stem cells and mix in a biological potpourri called Stromal Vascular Fraction or SVF. The cells are supposed to act like a rescue squad responding to an emergency (they find damage to the body and repair it).

Dr. Foglietti happily tells his patient, We have 7ccs. We have 39 million stem cells! The SVF is then reintroduced into Kyms body intravenously.

You just want to pray that this is something that will improve your quality of life, says Kym Sellers.

Although the procedure only takes a few hours, itll be months until Kym or the doctors can determine if it was successful. If it is, itll be used to treat everything from asthma to A.L.S. For now though, Kym waits and prays.

Just praying for the best, she says.

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Experimental procedure uses stem cells made from body fat

By William T. Koustas

The litigation between Regenerative Sciences, LLC (Regenerative) and FDA may have come to an end on Tuesday, February 4th, when the United States Court of Appeals for the District of Columbia Circuit ruled against Regenerative, concluding that FDA has the authority to regulate certain autologous stem cells procedures. The D.C. Circuit affirmed the lower courts decision granting summary judgment to the government, dismissing Regeneratives counterclaims, and permanently enjoining Regeneratives operations.

Regenerative is a Colorado company that owns a medical technique known as the Regenexx Procedure, a non-surgical procedure by which physicians take bone marrow and blood samples from a patient, culture the stem cells, mix the cultured cells with doxycycline, and inject the stem cell mixture back into the same patient in order to treat joint, muscle, tendon, or bone pain. The Regenexx Procedure is exclusively licensed for use by a Colorado clinic where its inventors practice.

Our prior blog posts on this case provide more background (see here andhere for example), but in essence, FDAs litigation stance was that the stem cell mixture used in the Regenexx Procedure was a drug under the Federal Food, Drug, and Cosmetic Act (FDCA), thus imposing current Good Manufacturing Practices (cGMP) and labeling requirements applicable to all drugs. On the other side, Regenerative argued that FDA had no authority over the Regenexx Procedure because it involved the practice of medicine, which is outside of FDAs purview, and because the stem cell mixture was not introduced or delivered for introduction into interstate commerce.

The D.C. Circuit upheld the district courts decision, frequently relying on long-standing principles of food and drug law. The court first found that the stem cell mixture met the definition of drug contained in the FDCA as it was an article derived mainly from human tissue intended to treat orthopedic diseases and to affect musculoskeletal function. Slip Op. at 6. In addition, and perhaps of more consequence, the court disagreed with Regeneratives argument that FDA was interfering with the practice of medicine by preventing physicians from performing autologous stem cell procedures. The D.C. Circuit described this argument as wide of the mark, clarifying that FDA was seeking to regulate the stem cell mixture and not the procedure itself. Id. at 7.

The court also rejected Regeneratives argument that FDA lacked jurisdiction over the stem cell mixture given that the Regenexx Procedure is performed entirely within the State of Colorado. Unsurprisingly, the court restated the well-known principle that the interstate commerce requirement of the FDCA is satisfied if a component of a product is shipped in interstate commerce prior to its administration to a patient. Id. at 9. The court also seemed to agree with FDAs position that the interstate commerce requirement could be satisfied simply because the stem cell mixture would undoubtedly have effects on interstate markets for orthopedic care . . . . Id. at 8.

The D.C. Circuit also dismissed Regeneratives argument that the stem cell mixture was a human cell, tissue, or cellular and tissue-based product (HCT/P), and thus exempt from manufacturing and labeling requirements. The court found that the stem cell mixture was likely more than minimally manipulated [b]ecause [Regenerative] concede[d] that culturing [stem cells] affects their characteristics and offer[ed] no evidence that those effects constitute only minimal manipulation, they fail to carry that burden as a matter of law. Id. at 12.

After summarily rejecting Regeneratives arguments, the D.C. Circuit ruled that the stem cell mixture was adulterated and misbranded. The court found that the stem cell mixture was adulterated because it was not manufactured in conformance with cGMP requirements, and that they were misbranded because the information on the label on the syringe that contains the stem cell mixture did not include adequate directions for use or bear the Rx only symbol. Id. at 14-15.

Although the court upheld the permanent injunction, it did so only after analyzing whether there was a reasonable likelihood of further violations in the future. Id. at 18. While the court determined that such likelihood existed in this case, this suggests that a violation of the FDCA, in and of itself, does not automatically necessitate injunctive relief but must be considered based on the facts of each case.

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D.C. circuit rules FDA can regulate autologous stem cells

PUBLIC RELEASE DATE:

6-Feb-2014

Contact: Becky Lindeman journal.pediatrics@cchmc.org 513-636-7140 Elsevier Health Sciences

Cincinnati, OH, February 6, 2014 -- Advances in neonatal care for very preterm infants have greatly increased the chances of survival for these fragile infants. However, preterm infants have an increased risk of developing bronchopulmonary dysplasia (BPD), a serious lung disease, which is a major cause of death and lifelong complications. In a new study scheduled for publication in The Journal of Pediatrics, researchers evaluated the safety and feasibility of using stem cell therapies on very preterm infants to prevent or treat BPD.

Won Soon Park, MD, PhD, and colleagues from Samsung Medical Center and Biomedical Research Institute, Seoul, Republic of Korea, conducted a phase I, single-center trial of intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells to nine very preterm infants (24-26 weeks gestational age) who were at high risk of developing BPD.

All patients who received the treatment tolerated the procedure well without any immediate serious adverse effects. Thirty-three percent of treated infants developed moderate BPD and none developed severe BPD, and 72 percent of a matched comparison group developed moderate or severe BPD. Another serious side effect of very preterm birth, retinopathy of prematurity requiring surgery, tended to occur less often in treated infants. Overall, all nine treated infants survived to discharge, and only three developed moderate BPD.

This phase I study suggests that intratracheal administration of mesenchymal stem cells is safe and feasible. According to Dr. Park, "These findings strongly suggest that phase II clinical trials are warranted to test the efficacy of mesencymal stem cell transplantation, which could lead to new therapies to prevent or cure BPD." Dr. Park and colleagues are currently conducting a long-term safety and follow-up study of these nine preterm infants (ClinicalTrials.gov: NCT01632475).

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Stem cells to treat lung disease in preterm infants

A new study, published today in the journal Applied Materials & Interfaces, has found a new method for growing human embryonic stem cells, that doesn't rely on supporting human or animal cells.

Traditionally, these stem cells are cultivated with the help of proteins from animals, which rules out use in the treatment of humans. Growing stem cells on other human cells risks contamination with pathogens that could transmit diseases to patients.

The team of scientists led by the University of Surrey and in collaboration with Professor Peter Donovan at the University of California have developed a scaffold of carbon nanotubes upon which human stem cells can be grown into a variety of tissues. These new building blocks mimic the surface of the body's natural support cells and act as scaffolding for stem cells to grow on. Cells that have previously relied on external living cells can now be grown safely in the laboratory, paving the way for revolutionary steps in replacing tissue after injury or disease.

Dr Alan Dalton, senior lecturer from the Department of Physics at the University of Surrey said: "While carbon nanotubes have been used in the field of biomedicine for some time, their use in human stem cell research has not previously been explored successfully."

"Synthetic stem cell scaffolding has the potential to change the lives of thousands of people, suffering from diseases such as Parkinson's, diabetes and heart disease, as well as vision and hearing loss. It could lead to cheaper transplant treatments and could potentially one day allow us to produce whole human organs without the need for donors."

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The above story is based on materials provided by University of Surrey. Note: Materials may be edited for content and length.

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New stem cell research removes reliance on human and animal cells

49 minutes ago This image shows iPS cells (green) generated using histone variants TH2A and TH2B and two Yamanaka factors (Oct3/4 and Klf4). Credit: RIKEN

One major challenge in stem cell research has been to reprogram differentiated cells to a totipotent state. Researchers from RIKEN in Japan have identified a duo of histone proteins that dramatically enhance the generation of induced pluripotent stem cells (iPS cells) and may be the key to generating induced totipotent stem cells.

Differentiated cells can be coaxed into returning to a stem-like pluripotent state either by artificially inducing the expression of four factors called the Yamanaka factors, or as recently shown by shocking them with sublethal stress, such as low pH or pressure. However, attempts to create totipotent stem cells capable of giving rise to a fully formed organism, from differentiated cells, have failed.

The study, published today in the journal Cell Stem Cell and led by Dr. Shunsuke Ishii from RIKEN, sought to identify the molecule in the mammalian oocyte that induces the complete reprograming of the genome leading to the generation of totipotent embryonic stem cells. This is the mechanism underlying normal fertilization, as well as the cloning technique called Somatic-Cell Nuclear Transfer (SCNT).

SCNT has been used successfully to clone various species of mammals, but the technique has serious limitations and its use on human cells has been controversial for ethical reasons.

Ishii and his team chose to focus on two histone variants named TH2A and TH2B, known to be specific to the testes where they bind tightly to DNA and affect gene expression.

The study demonstrates that, when added to the Yamanaka cocktail to reprogram mouse fibroblasts, the duo TH2A/TH2B increases the efficiency of iPSC cell generation about twentyfold and the speed of the process two- to threefold. And TH2A and TH2B function as substitutes for two of the Yamanaka factors (Sox2 and c-Myc).

By creating knockout mice lacking both proteins, the researchers show that TH2A and TH2B function as a pair, are highly expressed in oocytes and fertilized eggs and are needed for the development of the embryo after fertilization, although their levels decrease as the embryo grows.

In the early embryo, TH2A and TH2B bind to DNA and induce an open chromatin structure in the paternal genome, thereby contributing to its activation after fertilization.

These results indicate that TH2A/TH2B might induce reprogramming by regulating a different set of genes than the Yamanaka factors, and that these genes are involved in the generation of totipotent cells in oocyte-based reprogramming as seen in SCNT.

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Histones may hold the key to the generation of totipotent stem cells

As one of the follically-challenged, any new breakthroughs in the area of hair regeneration will generally get my attention. When stem cells first started to gain widespread media attention I, no doubt like many others, thought a full head of hair was just around the corner. But despite numerous developments, years later my dome is still of the chrome variety. Providing the latest cause for cautious optimism, researchers have now developed a way to generate a large number number of hair-follicle-generating stem cells from adult cells.

In what they claim is a world first, researchers from the University of Pennsylvania (UPenn) and the New Jersey Institute of Technology have developed a technique to convert adult human stem cells into epithelial stem cells (EpSCs).

By adding three genes to human skin cells called dermal fibroblasts that live in the dermis layer of the skin and generate connective tissue, a team led by Xiaowei "George" Xu, MD, PhD, at the Perelman School of Medicine was able to convert them into induced pluripotent stem cells (iPSCs). The iPSCs, which have the ability to differentiate into any cell type, were then converted into epithelial stem cells (EpSCs) that are normally found at the bulge of hair follicles.

Through careful control of the timing of delivery of growth factors to the cells, the researchers say they were able to turn over 25 percent of the iPSCs into EpSCs in 18 days. When they then mixed these EpSCs with mouse follicular inductive dermal cells and grafted them onto the skin of immunodeficient mice, functional human epidermis and follicles similar to hair follicles were produced.

"This is the first time anyone has made scalable amounts of epithelial stem cells that are capable of generating the epithelial component of hair follicles, said Xu, who added that these cells have many potential applications, including wound healing, cosmetics, and hair regeneration.

But some hurdles still need to be jumped before I make my first trip to the hairdresser in a decade. Xu points out that when a person loses hair, they lose not only epithelial cells, but also a kind of adult stem cell called dermal papillae. "We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet."

On a positive note, researchers from the Tokyo University of Science have reported promising results in reconstructing hair follicle germs from adult epithelial stem cells and cultured dermal papilla cells, so even though we haven't rounded the corner yet,it definitely seems to be getting closer.

The teams research is published in the journal Nature Communications.

Source: University of Pennsylvania

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Stem cell-based treatment for baldness a step closer

Durham, NC (PRWEB) February 04, 2014

STEM CELLS is proud to announce the appointment of new Associate Editor, Dr. Toru Kondo of Hokkaido University, Japan. Dr. Kondo has served as an outstanding member of the STEM CELLS Editorial Board since 2007 and we are delighted that he has accepted our invitation to become an Associate Editor. He joins Associate Editors, Dr. Majlinda Lako and Dr. Noel Buckley, Concise review Editor Dr. Terry Lappin, and Editor Dr. Jan Nolta.

Dr. Kondo brings a high level of additional expertise to our group of editors. In 2012 he was appointed as a full professor at the Institute for Genetic Medicine, Hokkaido University in Sapporo, Japan. His laboratory studies how neural stem/precursor cells are involved in the development of CNS diseases, such as brain tumor and Alzheimers disease. He is particularly interested in identifying new molecules associated with these disorders, characterizing them and developing new therapeutic methods. He has also a keen interest in the molecular mechanism of oligodendrocyte precursor cell differentiation. He hopes one day the knowledge gained from his work will contribute to the development of therapeutic applications.

Dr. Kondo had formerly been a group leader at the Cambridge University Centre for Brain Repair UK, a team leader at the RIKEN Center for Developmental Biology (CDB) Japan and a full professor at the Ehime University Proteo-Medicine Research Center Japan.

Dr. Kondo is replacing Associate Editor Dr. Mark Pittenger, who is stepping down at the end of his term. Dr. Pittenger has been fundamental in helping STEM CELLS remain at the top of the field. STEM CELLS is grateful for his contributions in the advancement of the Journal.

We welcome Dr. Kondo and the outstanding expertise that he brings to our editorial team and wish Dr. Pittenger all the best in the New Year.

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About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley-Blackwell.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS (http://www.StemCells.com), now in its 32nd year, is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST (http://www.TheOncologist.com), in its 19th year, is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE (http://www.StemCellsTM.com), in its third year, is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About Wiley-Blackwell: Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the worlds leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit http://www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the worlds most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

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Toru Kondo Named New Associate Editor of STEM CELLS

Research from Rutgers Cancer Institute of New Jersey demonstrates that using zebrafish to identify self-renewing tumor stem cells in prostate cancers may be more beneficial than using traditional experimental models when aiming to predict response to therapy. Prostate cancers are suggested to contain self-renewing tumor stem cells that have the ability to grow uncontrollably and spread. Identified as tumor-initiating cells (TICs), research has shown that these cells are found to be resistant to standard chemotherapy.A desirable treatment strategy is to develop therapies that would effectively target the self-renewing capabilities of the TICs, which requires better identification of TICs themselves. Utilizing prostate cancer samples from patients diagnosed at the Cancer Institute of New Jersey between 2008 and 2012, Cancer Institute investigators used mouse and zebrafish models to identify the frequencies of TICs from each patients prostate cancer cells. The research appears in the latest edition of The Prostate (DOI 10.1002/pros.22740).

Typically,TICs are identified through more mechanical methods, such as cell sorting or dye staining. Cancer Institute investigators developed a new method to enrich for TICs through remodeling of the environment of prostate cells in a laboratory setting by allowing them to adhere to collagen a glue-like protein that holds together skin, connective, and prostate tissues in the human body. In collaboration between multiple Cancer Institute laboratories, prostate tumors cells from patients are first identified with fluorescent markers in the laboratory of Cancer Institute Director, Robert S. Di- Paola, M.D., professor of medicine at Rutgers Robert Wood Johnson Medical School.These tumor cells are then enriched for TICs by collagen adhesion at the laboratory of the Cancer Institute Chief Scientific Officer, Joseph R. Bertino, M.D., university professor of medicine and pharmacology at Robert Wood Johnson Medical School.The TIC frequencies for these tumor cells are then examined in mice and zebrafish assays.

When these TICs were transplanted into both mice and zebrafish embryos, it was determined that a fraction of the cells that had adhesive properties had the potential for tumor development and for tumor spread.The authors found that this detection was better determined within the zebrafish model, due to its translucent nature allowing for noninvasive observation and also due to lack of immune response to tumor cells. It is a research model senior author and Cancer Institute scientist Hatem E. Sabaawy, M.D., Ph.D., says holds great value.The self-renewing properties found in prostate TICs are regulated through molecular pathways within the cell. By targeting these pathways and using a few cells from each patient, there may be an opportunity to control progression and recurrence in multiple cancers.The zebrafish model enables researchers to examine this pathway to progression in real time, thus having the potential to serve as a better tool for personalized cancer therapy, noted Dr. Sabaawy, who is also an assistant professor of medicine at Robert Wood Johnson Medical School.

Along with Sabaawy and Drs. Di- Paola and Bertino, the author team consists of Nitu Bansal, Cancer Institute; Stephani Davis, Robert Wood Johnson Medical School; Irina Tereshchenko and Tulin Budak-Alpdogan, Cancer Institute; Hua Zhong, Robert Wood Johnson Medical School; and Mark N. Stein and Isaac Yi Kim, Cancer Institute and Robert Wood Johnson Medical School.

The study was supported in part by grants from the Department of Defense (Prostate Cancer Grant W81XWH-12-1-0251 to Sabaawy, Bertino, and Kim), the National Cancer Institute (Cancer Center Support Grant Award P30CA072720 to Di- Paola), and the Cancer Institute (Pilot Grant to Bertino and Sabaawy).

Rutgers Cancer Institute of New Jersey (www.cinj.org) is the states first and only National Cancer Institute designated Comprehensive Cancer Center.As part of Rutgers,The State University of New Jersey, the Cancer Institute of New Jersey is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention. Physician scientists at the Cancer Institute engage in translational research, transforming their laboratory discoveries into clinical practice, bringing research to life.

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Zebrafish model is useful tool in identifying self-renewing properties of prostate cancer stem cells

Few medical discoveries have held the great promise of stem cells to regenerate nerves, organs and tissue damaged by disease, heredity or injury. Basically, the stem cells could replicate any other cell in the body, offering immense hope that were still anxiously waiting to be realized of curing Alzheimers, making damaged spinal cords whole, treating kidney, liver and lung disease and making damaged hearts whole.

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EDITORIAL: Stem-cell discovery addresses ethical issues