Category Archives: Stem Cells

Blind mice have been able to see once more in a laboratory exploit that marks a further boost for the fast-moving field of retinal therapy, according to a study published on Sunday.

Scientists in Britain used stem cells -- early-stage, highly versatile cells -- taken from mice embryos, and cultured them in a lab dish so that they differentiated into immature photoreceptors, the light-catching cells in the retina. Around 200,000 of these cells were then injected into the retinas of mice; some cells integrated smoothly with local cells to restore sight. The rodents were put through their paces in a water maze and examined by optometry to confirm that they responded to light.

Embryonic stem cells "could in future provide a potentially unlimited supply of health photoreceptors for retinal transplantations to treat blindness in humans," Britain's Medical Research Council (MRC) said in a press release. Photoreceptor loss lies behind degenerative eye diseases such as retinitis pigmentosa and age-related macular degeneration, also called AMD.

Stem cells have triggered a huge interest and investment on the back of hopes that they can become replacement tissue, grown in a lab dish, for cells damaged by disease or accident. But the exciting field has to overcome big obstacles. One is the ability to coax these immature cells into safely becoming the specialized cells that are needed, rather than turn cancerous.

This is where the new work marks a gain, according to lead researcher Robin Ali at the University College London Institute of Ophthalmology and Moorfields Eye Hospital. His team previously found that sight could be restored in blind mice by transplanting immature photoreceptors called rod cells that were taken from the retinas of healthy rodents.

The latest research takes things further because the transplanted material comprises all the different nerve cells needed for sight -- and they were not taken from other animals. Instead, they were grown in a lab and differentiated into the right cells thanks to a new technique, pioneered in Japan, that replicates the shape of the retina.

"Over recent years, scientists have become pretty good at working with stem cells and coaxing them to develop into different types of adult cells and tissues," said Ali.

"But until recently, the complex structure of the retina has proved difficult to reproduce in the lab. This is probably because the type of cell culture we were using was not able to recreate the developmental process that would happen in a normal embryo."

Ali added: "The next step will be to refine this technique using human cells to enable us to start clinical trials."

The study appears in the journal Nature Biotechnology.

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Stem Cells Help Blind Mice See

WASHINGTON Chinese researchers said Thursday they have developed an "easy and safe way" to create stem cells, a breakthrough that could greatly promote the development of so-called therapeutic cloning to generate tissues and organs for treatment of diseases.

The method, described in the U.S. journal Science, involved a cocktail of small-molecule compounds to reprogram somatic cells to a pluripotent state with the ability to differentiate into any other type of cell in the body.

Previously, the genetic manipulation required to induce this pluripotent state, via nuclear transfer into oocytes or through the ectopic expression of defined factors, is complicated, a fact that has limited the cells' clinical applications so far.

In this study, Professor Deng Hongkui of Peking University said his team validated "a whole new route" to pluripotent stem cells by inducing a pluripotent state in mouse somatic cells with a combination of seven small-molecule compounds.

"Small molecules have advantages because they can be cell permeable, non-immunogenic, more cost-effective, and can be more easily synthesized, preserved, and standardized," the researchers wrote in their paper.

"Moreover, their effects on inhibiting and activating the function of specific proteins are often reversible and can be finely tuned by varying the concentrations," they said.

In total, pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2 percent using the combination of small-molecule compounds, the researchers found.

To characterize their differentiation potential, they injected the chemically induced pluripotent stem cells (CiPSCs) into immunodeficient mice and found that the cells were able to differentiate into tissues of all three germ layer.

Unlike mice generated through traditional methods, the mice generated from CiPSCs were "100 percent viable and apparently healthy for up to 6 months," they said.

Using the CiPSCs technology, the researchers have successfully created several healthy laboratory mice from fibroblastic cells in the adult mouse lung, including one called QingQing, Deng wrote in an email.

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Chinese researchers find simple way to create stem cells

AHMEDABAD: Insulin-making stem cells derived from fat in the abdominal wall have shown to decrease insulin doses for diabetics by an average of 50%, experts at Institute of Kidney Diseases and Research Center (IKDRC) claimed here on Thursday.

Dr H L Trivedi, director of IKDRC, said that a paper with data of 20 insulin-dependent diabetics who responded well to Insulin Secreting Cells (ISC) implanted in them was presented at the International Cell Transplant Society's Congress in Milan recently.

"Insulin-making stem cells were generated from Adipose Tissue Derived Mesenchymal Stem Cells (ADMSC) found in the abdominal wall. These fat cells underwent trans-differentiation in the laboratory to be made into stems cells which will produce insulin. The stem cells were injected into the thymus, skin and a major portion into the liver. These cells were found to reduce insulin requirement by an average of 50%," said Dr Trivedi.

Dr Aruna Vanikar, head of the IKDRC pathology department, said that the study included initial data of five city-based diabetes patients with chronic renal failure who were subjected to double stem cell infusion of ISC and MSC with hematopoietic stem cells. "All these patients have done well with minimum immuno-suppression, zero rejection and reduction in insulin requirement to about 50% of their original need before kidney failure," said Dr Vanikar.

Dr Vanikar said that the study was well received by the international community. "The next level will be to broaden the study and work towards making stem cells which render patients completely drug free".

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Stem cells can halve insulin dosage: IKDRC study

July 19, 2013 Stem cells are key to the promise of regenerative medicine: the repair or replacement of injured tissues with custom grown substitutes. Essential to this process are induced pluripotent stem cells (iPSCs), which can be created from a patient's own tissues, thus eliminating the risk of immune rejection. However, Shinya Yamanaka's formula for iPSCs, for which he was awarded last year's Nobel Prize, uses a strict recipe that allows for limited variations in human cells, restricting their full potential for clinical application.

Now, in this week's issue of Cell Stem Cell, the Salk Institute's Juan Carlos Izpisua Belmonte and his colleagues show that the recipe for iPSCs is far more versatile than originally thought. For the first time, they have replaced a gene once thought impossible to substitute, creating the potential for more flexible recipes that should speed the adoption of stem cells therapies.

Stem cells come in two types: embryonic stem cells (ESCs), which are immature cells that have never differentiated into specific cell types, and induced pluripotent stem cells, which are mature cells that have been reprogrammed back into an undifferentiated state. After the initial discovery in 2006 by Yamanaka that introducing four different genes into a mature cell could suffice for reprogramming the cell to pluripotency, most researchers adopted his recipe.

Izpisua Belmonte and his colleagues took a fresh approach and discovered that pluripotency (the stem cell's ability to differentiate into nearly any kind of adult cell) can also be accomplished by balancing the genes required for differentiation. These genes code for "lineage transcription factors," proteins that start a stem cell down the path to differentiate first into a particular cell lineage, or type, such as a blood cell versus a skin cell, and then finally into a specific cell, such as a white blood cell.

"Prior to this series of experiments, most researchers in the field started from the premise that they were trying to impose an 'embryonic-like' state on mature cells," says Izpisua Belmonte, who holds the Institute's Roger Guillemin Chair. "Accordingly, major efforts had focused on the identification of factors that are typical of naturally occurring embryonic stem cells, which would allow or further enhance reprogramming."

For the first time, the Belmonte laboratory has replaced OCT4, one gene previously thought indispensable for the reprogramming of human cells into embryonic-like cells.

Despite these efforts, there seemed to be no way to determine through genetic identity alone that cells were pluripotent. Instead, pluripotency was routinely evaluated by functional assays. In other words, if it acts like a stem cell, it must be a stem cell.

That condition led the team to their key insight. "Pluripotency does not seem to represent a discrete cellular entity but rather a functional state elicited by a balance between opposite differentiation forces," says Izpisua Belmonte.

Once they understood this, they realized the four extra genes weren't necessary for pluripotency. Instead, it could be achieved by altering the balance of "lineage specifiers," genes that were already in the cell that specified what type of adult tissue a cell might become.

"One of the implications of our findings is that stem cell identity is actually not fixed but rather an equilibrium that can be achieved by multiple different combinations of factors that are not necessarily typical of ESCs," says Ignacio Sancho-Martinez, one of the first authors of the paper and a postdoctoral researcher in Izpisua Belmonte's laboratory.

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More versatile approach to creating stem cells discovered

July 19, 2013

Stem cell studies are producing some of the most promising research results for replacing or regenerating damaged tissue, and a new study from a team of Spanish and American scientists has described a more flexible approach to creating the valuable cells.

Nobel Prize laureate Shinya Yamanaka developed the initial formula for developing induced pluripotent stem cells (iPSCs), or stem cells created by reverse-engineering a patients own cells. The Nobel-winning formula is a stringent recipe that allows for a narrow degree of variations in human cells.

To determine the success of Yamanakas method, stem cells pluripotency or the ability to differentiate into other types of cells was evaluated by functional assays, meaning if it acts like a stem cell, then it is a stem cell.

The new study, which appeared in the journal Cell Stem Cell, turned this assumption-based analysis on its head. Led by the Salk Institutes Juan Carlos Izpisua Belmonte, the team realized pluripotency is not a type of cell, but a state achieved by a balance of opposing differentiation forces.

Prior to this series of experiments, most researchers in the field started from the premise that they were trying to impose an embryonic-like state on mature cells, said Belmonte. Accordingly, major efforts had focused on the identification of factors that are typical of naturally occurring embryonic stem cells, which would allow or further enhance reprogramming.

Once the team realized the pursuit of an embryonic-like state wasnt essential, they were able to question the changes to four genes believed to be necessary to the process according to the prevailing method. Instead, the team found that changing the equilibrium of lineage specifier genes already found in a patients cell could induce pluripotency.

One of the implications of our findings is that stem cell identity is actually not fixed but rather an equilibrium that can be achieved by multiple different combinations of factors that are not necessarily typical of (stem cells taken from embryos), said study co-author Ignacio Sancho-Martinez, a postdoctoral researcher at the Salk Institute.

According to the study, seven additional genes can allow for the reprogramming of cells to iPSCs. The team was also able to replace a gene from the original method called Oct4, which was thought to be indispensable to the process. Along with replacing another gene once thought essential, called SOX2, the researchers showed a completely different way for conceptualizing stem cell development.

It was generally assumed that development led to cell/tissue specification by opening certain differentiation doors, said Emmanuel Nivet, a post-doctoral researcher at the Salk Institute.

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Researchers Take More Nuanced Approach To Making Stem Cells

Public release date: 18-Jul-2013 [ | E-mail | Share ]

Contact: Ingrid L. Thomas ithomas@iadr.org 703-299-8084 International & American Associations for Dental Research

Alexandria, Va., USA Today, the International and American Associations for Dental Research (IADR/AADR) published a paper titled "Gingivae Contain Neural-crest- and Mesoderm-derived Mesenchymal Stem Cells." The paper, written by lead author Songtao Shi, Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, USA, is published in the OnlineFirst portion of the IADR/AADR Journal of Dental Research.

Gingivae represent a unique soft tissue that serves as a biological barrier to cover the oral cavity side of the maxilla and mandible. Recently, the gingivae were identified as containing mesenchymal stem cells (GMSCs). However, it is unknown whether the GMSCs are derived from cranial neural crest cells (CNCC) or the mesoderm.

In this study, Shi and his team of researchers demonstrated that around 90 percent of GMSCs are derived from CNCC and 10 percent from the mesoderm. In comparison with mesoderm MSCs (M-GMSCs), CNCC-derived GMSCs (N-GMSCs) show an elevated capacity to differentiate into neural cells and chondrocytes as well as to modulate immune cells. When transplanted into mice with dextran sulfate sodium-induced colitis, N-GMSCs showed superior effects in ameliorating inflammatory-related disease phenotype in comparison with the M-GMSC treatment group.

Further research is required to understand the interaction between the neural crest cell derived and mesoderm derived gingivae mesenchymal stem cells (N-GMSCs and M-GMSCs) in terms of their functional roles in gingival immune defense and wound healing.

"The tooth and surrounding tissues are a rich source of stem cells, and this JDR manuscript demonstrates that gingivae contain highly proliferative stem cells from two different embryonic origins and that these cells exhibit distinct behaviors," said JDR Associate Editor Jacques Nr. "These results suggest that gingivae, an easily accessible tissue, are an attractive source for stem cells that can be used in tissue regeneration."

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Visit http://jdr.sagepub.com/content/early/recent to read the JDR manuscript titled "Gingivae Contain Neural-crest- and Mesoderm-derived Mesenchymal Stem Cells" or contact Ingrid L. Thomas at ithomas@iadr.org to request the PDF.

About the Journal of Dental Research

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New research suggests that gingival stem cells can be used in tissue regeneration