Category Archives: Stem Cells

7 hours ago A new method resulted in a colony of stem cells, glowing green, derived from one adult immune cell. Credit: Laboratory of Matthias Stadtfeld at NYU Langone Medical center

Scientists at NYU Langone Medical Center have found a way to boost dramatically the efficiency of the process for turning adult cells into so-called pluripotent stem cells by combining three well-known compounds, including vitamin C. Using the new technique in mice, the researchers increased the number of stem cells obtained from adult skin cells by more than 20-fold compared with the standard method. They say their technique is efficient and reliable, and thus should generally accelerate research aimed at using stem cells to generate virtually any tissue. Stem cells are immature or uncommitted cells that are theoretically capable of becoming any cell type.

"This big boost in efficiency gives us an opportunity now to study stem cell programming mechanisms at high resolution," says Matthias Stadtfeld, PhD, assistant professor of cell biology and a member of the Skirball Institute of Biomolecular Medicine and the Helen L. and Martin S. Kimmel Center for Stem Cell Biology at NYU Langone Medical Center, who led the research.

"This is a very exciting advance," says Ruth Lehmann, PhD, director of the Kimmel Center for Stem Cell Biology and the Skirball Institute at NYU Langone and chair of the Department of Cell Biology. "The new technology developed by the Stadtfeld lab to reprogram differentiated cells efficiently and effectively brings the prospect of stem cell technology for safe use in regenerative medicine ever so much closer."

The standard method for reprogramming skin, blood, or other tissue-specific cell types into "induced pluripotent stem cells" (iPSCs) was reported in 2006 by the laboratory of Kyoto University's Shinya Yamanaka, who later won a Nobel Prize for the achievement. The method involves the artificial expression of four key genes dubbed OKSM (for Oct4, Klf4, Sox2 and myc) whose collective activity slowly prods cells into an immature state much like that of an early embryonic cell.

In principle, one could take a sample of cells from a person, induce the cells to become iPSCs, then multiply the iPSCs in a lab dish and stimulate them to mature towards desired adult cell types such as blood, brain or heartwhich then could be used to replace injured or diseased tissue in that same individual.

But there are many formidable technical obstacles, among which is the low efficiency of currently used protocols. Converting most cell types into stable iPSCs occurs at rates of 1 percent or less, and the process can take weeks.

Researchers throughout the world have been searching for ways to boost this efficiency, and in some cases have reported significant gains. These procedures, however, often alter vital cellular genes, which may cause problems for potential therapies. For the new study, reported online today in Stem Cell Reports, Dr. Stadtfeld and his laboratory team decided to take a less invasive approach and investigate chemical compounds that transiently modulate enzymes that are present in most cells. "We especially wanted to know if these compounds could be combined to obtain stem cells at high efficiency," Dr. Stadtfeld says.

Two of these compounds influence well known signaling pathways, called Wnt and TGF-, which regulate multiple growth-related processes in cells. The third is vitamin C (also known as ascorbic acid). Best known as a powerful antioxidant, the vitamin was recently discovered to assist in iPSC induction by activating enzymes that remodel chromatinthe spiral scaffold for DNAto regulate gene expression.

Simon Vidal, a graduate student in the Stadtfeld lab, and Bhishma Amlani, a postdoctoral researcher, looked first at mouse skin fibroblasts, the most common cell type used for iPSC research. Adding to fibroblasts engineered to express OKSM either vitamin C, a compound to activate Wnt signaling, or a compound to inhibit TGF- signaling increased iPSC-induction efficiency weakly to about 1% after a week of cell culture. Combining any two worked a bit better. But combining all three brought the efficiency to about 80 percent in the same period of time.

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Team reports reliable, highly efficient method for making stem cells

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Newswise Investigators from the Institute for Research in Immunology and Cancer (IRIC) at the Universit de Montral have just published, in the prestigious magazine Science, the announcement of the discovery of a new molecule, the first of its kind, which allows for the multiplication of stem cells in a unit of cord blood. Umbilical cord stem cells are used for transplants aimed at curing a number of blood-related diseases, including leukemia, myeloma and lymphoma. For many patients this therapy comprises a treatment of last resort.

Directed by Dr. Guy Sauvageau, principal investigator at IRIC and hematologist at the Maisonneuve-Rosemont Hospital, this world breakthrough has the potential to multiply by 10 the number of cord blood units available for a transplant in humans. In addition, it will considerably reduce the complications associated with stem cell transplantation. And it will be particularly useful for non-Caucasian patients for whom compatible donors are difficult to identify.

A clinical study using this molecule, named UM171 in honor of the Universit de Montral, and a new type of bioreactor developed for stem culture in collaboration with the University of Toronto will be initiated in December 2014 at the Maisonneuve-Rosemont Hospital.

According to Dr. Guy Sauvageau, This new molecule, combined with the new bioreactor technology, will allow thousands of patients around the world access to a safer stem cell transplant. Considering that many patients currently cannot benefit from a stem cell transplant for lack of matching donors, this discovery looks to be highly promising for the treatment of various types of cancer.

The Centre of Excellence for Cellular Therapy at the Maisonneuve-Rosemont Hospital will serve as production unit for these stem cells, and grafts will then be distributed to patients in Montreal, Quebec City and Vancouver for this first Canadian clinical study. Tangible results should be available one year later, that is, in December 2015. The significance of this new discovery is such that over time, conclusive clinical results could revolutionize the treatment of leukemia and other blood-related illnesses.

These extraordinary advances result from the efforts of a remarkable team that includes extremely gifted students and postdoctoral investigators working in the IRIC laboratories, adds Dr. Guy Sauvageau. Among them, the first authors of this publication: Iman Fars, doctoral student, and Jalila Chagraoui, research officer, along with the professionals in IRICs medical chemistry core facility under the direction of Anne Marinier, who optimized the therapeutic properties of this new molecule.

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Umbilical cord blood from newborn children is an excellent source of hematopoietic stem cells for stem cell transplants, since their immune system is still immature and the stem cells have a lower probability of inducing an adverse immune reaction in the recipient.

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World Breakthrough: A New Molecule Allows for an Increase in Stem Cell Transplants

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12-Sep-2014

Contact: Peggy Murphy pemurphy@luriechildrens.org 773-755-7485 Children's Memorial Hospital

Metastatic melanoma is a highly aggressive skin cancer whose incidence is on the rise at an alarming rate. Research has revealed that metastatic tumor cells share similar signaling pathways with embryonic stem cells to sustain plasticity and growth. However, major regulators of these pathways are often missing in tumor cells, thus allowing uncontrolled tumor growth and spreading to occur.

During early vertebrate development, Nodal, an embryonic growth factor that governs the growth, pattern and position of tissues, is critical for normal maturation. Nodal plays a significant role in maintaining the pluripotency of embryonic stem cells, meaning the ability of stem cells to differentiate into any of the three germ layers that comprise the body. The recent discovery of Nodal's re-expression in several aggressive and metastatic cancers has highlighted its critical role in self-renewal and maintenance of the stem cell-like characteristics of tumor cells such as melanoma. However, the signaling pathway receptors utilized by melanoma cells to propagate Nodal's effect remain(s) mostly anecdotal and unexplored.

The laboratory of Mary J.C. Hendrix, PhD made the novel discovery that embryonic stem cells and metastatic melanoma cells share a similar repertoire of receptors known as Type I serine/threonine kinase(s), but diverge in their Type II receptor expression. Further testing indicated that metastatic melanoma cells and embryonic stem cells use different receptors for Nodal signal transduction. These findings reveal the divergence in Nodal signaling between embryonic stem cells and metastatic melanoma that can impact new therapeutic strategies targeting the re-emergence of embryonic pathways in cancer.

This work is published in the International Journal of Cancer. Mary J.C. Hendrix, PhD points out: "Nodal-expressing tumor cells don't respond favorably to conventional therapies, supporting the premise that a combinatorial approach to targeting Nodal subpopulations within tumors, along with a front-line therapy, would constitute a more rational approach for treating aggressive cancer". Zhila Khalkhali-Ellis, PhD, senior research scientist in the Hendrix laboratory and the lead author says: "Our discoveries are important for advanced stage aggressive melanoma. Given that limited therapeutic options are currently available for this cancer, we have the opportunity to investigate whether the receptors can be modulated so that the signaling molecule can be neutralized to decrease aggressive behavior." The research was supported by the National Institutes of Health.

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Zhila Khalkhali-Ellis, PhD is Research Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine; and a member of the Cancer Biology and Epigenomics Program of Stanley Manne Children's Research Institute, affiliated with Ann & Robert H. Lurie Children's Hospital of Chicago.

Mary J.C. Hendrix, PhD is President & Scientific Director of Manne Research Institute; Children's Research Fund Professor; William G. Swartchild, Jr. Distinguished Research Professor at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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Re-expression of an embryonic signaling pathway in Melanoma utilizes different receptors

MIAMI (PRWEB) September 15, 2014

Global Stem Cells Group, Inc. has signed an exclusive representative contract with Consortia Innovas, SA, a Santiago, Chile-based health management, development and biotech company. Founded by entrepreneur Enrique Testart, M.D., Consortia Innovas focuses on helping patients gain access to the latest medical treatments regenerative medicine has to offer.

According to Global Stem Cells Group Founder Benito Novas, Testart searches the globe for innovative stem cell companies that fit in with the Chilean markets, and Global Stem Cells Group turned out to be a perfect fit. Innovas will be in charge of all Global Stem Cells Group divisions and programs in Chile, including patient recruiting through Regenestem, physician training and certification trough Stem Cell Training, and stem cell equipment and disposables sales through Adimarket.

Regenestem, Stem Cell Training and Adimarket are all subsidiaries of the Global Stem Cells Group brand.

Our main objective is to organize Chiles first symposium on Stem Cells and Regenerative Medicine in Santiago in early 2015, Novas says. Our new alliance with Consortia Innovas will allow us to establish our brand as the leader in regenerative medicine therapies in Chile.

The first annual Global Stem Cells Symposium is scheduled to take place in Buenos Aires Oct 2, 2014, to be preceded by an intensive two-day hands-on training course in stem cell harvesting, isolation and applications Sept. 27 and 28 at Santiagos Innovas facilities.

The key to Global Stem Cells Groups strategy to expand into foreign markets by recruiting local representatives and distributors like Consortia Innovas to help manage the companys growth in a specific geographic area. Global Stem Cells group requires any company under consideration for the expansion program to have more than five years experience in the health care industry with at least some experience in the field of regenerative medicine .

In addition, geographic alliances require a commitment to a number of stem cell training courses during a one-year period, certification of physicians, and willingness to organize a large medical meeting or symposium in their territory.

To learn more about the Global Stem Cells Group alliance with Consortia Innovas, SA, visit http://www.stemcellsgroup.com, email bnovas(at)stemcellsgroup(dot)com, or call 305.224.1858.

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Global Stem Cells Group Signs Consortia Innovas, SA to Exclusive Representative Contract for Chile Territory

Surgeons implanted retinal tissue created after reverting the patient's own cells to a "pluripotent" state

Researchers were able to grow sheets of retinal tissue from induced pluripotent stem cells, and have now implanted them for the first time in a patient. Credit: RIKEN/Foundation for Biomedical Research and Innovation

A Japanese woman in her 70s is the world's first recipient of cells derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

In a two-hour procedure starting at 14:20 local time today, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.

The procedure took place at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the epithelium sheets. She derived them from the patient's skin cells, after producing induced pluripotent stem (iPS) cells and then getting them to differentiate into retinal cells.

Afterwards, the patient experienced no effusive bleeding or other serious problems, RIKEN has reported.

The patient took on all the risk that go with the treatment as well as the surgery, Kurimoto said in a statement released by RIKEN. I have deep respect for bravery she showed in resolving to go through with it.

He hit a somber note in thankingYoshiki Sasai, a CDB researcher who recenty committed suicide. This project could not have existed without the late Yoshiki Sasais research, which led the way to differentiating retinal tissue from stem cells.

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at Kyoto University without whose discovery of iPS cells, this clinical research would not be possible. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for that work.

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see 'Next-generation stem cells cleared for human trial').

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Next-Generation Stem Cells Transplanted in Human for the First Time

University of British Columbia, in collaboration with BetaLogics Venture, a division of Janssen Research & Development, LLC, has published a study highlighting a protocol to convert stem cells into insulin-producing cells. The new procedure could be an important step in the fight against Type 1 diabetes.

The protocol can turn stem cells into reliable, insulin-producing cells in about six weeks, far quicker than the four months it took using previous methods.

"We are a step closer to having an unlimited supply of insulin-producing cells to treat patents with Type 1 diabetes," says Timothy Kieffer who led the research and is a professor in UBC's Department of Cellular and Physiological Sciences and the Department of Surgery.

The protocol transforms stem cells into insulin-secreting pancreatic cells via a cell-culture method. The conversion is completed after the cells are transplanted into a host.

"We have not yet made fully functional cells in a dish, but we are very close," says Kieffer. "The cells we make in the lab produce insulin, but are still immature and need the transplant host to complete the transformation into fully functioning cells."

An important next step for UBC researchers and their industry collaborators is to determine how to prevent the insulin-producing cells' from being rejected by the body.

The research was published Sept. 11, in the journal Nature Biotechnology.

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

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Faster way found to create insulin-producing cells

Researchers at EMBL-EBI have resolved a long-standing challenge in stem cell biology by successfully 'resetting' human pluripotent stem cells to a fully pristine state, at point of their greatest developmental potential. The study, published in Cell, involved scientists from the UK, Germany and Japan and was led jointly by EMBL-EBI and the University of Cambridge.

Embryonic stem (ES) cells, which originate in early development, are capable of differentiating into any type of cell. Until now, scientists have only been able to revert 'adult' human cells (for example, liver, lung or skin) into pluripotent stem cells with slightly different properties that predispose them to becoming cells of certain types. Authentic ES cells have only been derived from mice and rats.

"Reverting mouse cells to a completely 'blank slate' has become routine, but generating equivalent nave human cell lines has proven far more challenging," says Dr Paul Bertone, Research Group Leader at EMBL-EBI and a senior author on the study. "Human pluripotent cells resemble a cell type that appears slightly later in mammalian development, after the embryo has implanted in the uterus."

At this point, subtle changes in gene expression begin to influence the cells, which are then considered 'primed' towards a particular lineage. Although pluripotent human cells can be cultured from in vitro fertilised (IVF) embryos, until now there have been no human cells comparable to those obtained from the mouse.

Wiping cell memory

"For years, it was thought that we could be missing the developmental window when nave human cells could be captured, or that the right growth conditions hadn't been found," Paul explains. "But with the advent of iPS cell technologies, it should have been possible to drive specialised human cells back to an earlier state, regardless of their origin -- if that state existed in primates."

Taking a new approach, the scientists used reprogramming methods to express two different genes, NANOG and KLF2, which reset the cells. They then maintained the cells indefinitely by inhibiting specific biological pathways. The resulting cells are capable of differentiating into any adult cell type, and are genetically normal.

The experimental work was conducted hand-in-hand with computational analysis.

"We needed to understand where these cells lie in the spectrum of the human and mouse pluripotent cells that have already been produced," explains Paul. "We worked with the EMBL Genomics Core Facility to produce comprehensive transcriptional data for all the conditions we explored. We could then compare reset human cells to genuine mouse ES cells, and indeed we found they shared many similarities."

Together with Professor Wolf Reik at the Babraham Institute, the researchers also showed that DNA methylation (biochemical marks that influence gene expression) was erased over much of the genome, indicating that reset cells are not restricted in the cell types they can produce. In this more permissive state, the cells no longer retain the memory of their previous lineages and revert to a blank slate with unrestricted potential to become any adult cell.

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Scientists revert human stem cells to pristine state

A new type of human stem cell, never seen in nature, has been made in the lab. The cells may be the primordial embryonic cell from which all our cells are created. They should be better at making replacement organs than existing stem cells.

"We see it as a blank canvas, the starting point for all tissues in the body," says Austin Smith of the University of Cambridge, who led the team that developed the cells.

It is a big claim, and the stem cell field has been rocked by false ones in recent times. Supposedly revolutionary procedures have turned out to be flawed, most recently the claim in Nature earlier this year that adult cells could be turned into stem cells simply by exposing them to acid. Science and Cell rejected the "STAP cells" papers, but Nature accepted them only to be forced to retract them in July.

However, Smith's findings are getting cautious support. "There are great people contributing to this paper, and their reputations are on the line," says Chris Mason of University College London. "I would be really surprised if it's not the real deal."

In theory stem cells can develop into any kind of cell, so they could be used to repair damaged organs or even build them from scratch. But most stem cells aren't that flexible. The best ones are "pluripotent", meaning they can turn into anything. Such cells have to be taken from embryos, which is controversial, or made by reverting adult cells to their embryonic state, called induced pluripotent stem cells.

But these pluripotent stem cells still carry genetic baggage from their previous existence. For instance, genes may have been activated for a particular course of development into a kidney, say or turned off by a chemical marking process called methylation.

"This [baggage] has been one of the confounding problems in this area," says Smith. The cells aren't completely neutral about what they develop into, and they are all different so can't be standardised.

The new cells have had their cellular memories wiped clean. Their genes have been cleansed of most methylation markers, so they behave more predictably and transform more consistently into other tissues. The team hopes that this will make them a better building block for organs and tissues than existing embryonic stem cells.

"Nothing has been written or drawn on them to tell them what to do or become," says Smith. "These cells could be a better and more pristine starting point."

Called naive stem cells, these have long been known in mice and rats, but they have never been found in humans.

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Ultimate human stem cells created in the lab

London, Sept 14:

Scientists have created a new type of human stem cell in the lab which they believe will be better at making replacement organs than existing stem cells.

In theory stem cells can develop into any kind of cell, so they could be used to repair damaged organs or even build them from scratch. But most stem cells are not that flexible, researchers said.

The best ones are pluripotent, meaning they can turn into anything. Such cells have to be taken from embryos or made by reverting adult cells to their embryonic state, called induced pluripotent stem cells, New Scientist reported.

But these pluripotent stem cells still carry genetic baggage from their previous existence. This ([baggage) has been one of the confounding problems in this area, said Austin Smith of the University of Cambridge, who led the team that developed the new cells.

The new cells have had their cellular memories wiped clean. Their genes have been cleansed of most methylation markers, so they behave more predictably and transform more consistently into other tissues.

The team hopes that this will make them a better building block for organs and tissues than existing embryonic stem cells.

Nothing has been written or drawn on them to tell them what to do or become. These cells could be a better and more pristine starting point, said Smith.

Called naive stem cells, these have long been known in mice and rats, but they have never been found in humans.

To make them, Smith and his colleagues mimicked the process that creates their mouse counterparts. They gave human embryonic stem cells extra copies of two genes, Nanog and Klf2, which triggered the gene network needed to make the naive cells.

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New type of human stem cell created in lab

Fibroblast Growth Factor FGF Stem Cells

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Fibroblast Growth Factor FGF & Stem Cells - Video