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Scientists reprogram stem cells to improve transplant effectiveness.

Stem cell scientists in China have used a technique known as de-differentiation to re-engineer cells to a more primitive state that increases cell survival rates and offers greater potential for clinical use.

The research was led by Dr. Hsiao Chang Chan of the Chinese University of Hong Kong.

Research into differentiation has led to a variety of breakthroughs as stem cell researchers harvest cells from one part of the body and genetically adapt them to fulfill a specialized role. However, if the implanted cells are too much like the cells of the targeted area they may not have the plasticity to engraft and repair the injured tissue.

"Stem cell differentiation and transplantation has been shown to improve function in conditions including degenerative diseases and blood supply disorders," Chan said. "However, the survival rate of transplanted cells in patients limits their overall effectiveness, which is a barrier to clinical use."

To overcome this issue, Chan's team explored de-differentiation, a process that reverts specialized, differentiated cells back to a more primitive cell.

The team focused their research on multipotent stem cells, (MSCs) which can be altered into a variety of cell types through differentiation. Bone marrow MSCs have the potential to differentiate into each of the three basic types of lineage cells which form bone (osteocytes), cartilage (chondrocytes) and fat tissue (adipocytes).

The team first differentiated bone marrow MSCs towards a neuronal lineage, but then removed the differentiation conditions, allowing the cell to revert back to a form with more basic cellular characteristics.

Following this process the team recorded increased cell survival rates following transplants. In an animal model de-differentiated cells were found to be more effective in improving cognitive functions and in aiding recovery from strokes, compared to unmanipulated stem cells both in living specimens and in laboratory experiments.

The results confirm that de-differentiation is a workable technique for reengineering cells to an earlier, more primitive state but reprogrammed to have increased cell survival rates and therefore their potential for clinical use.

"The finding that MSCs can be reprogrammed to have enhanced survival and therapeutic efficacy in an animal model with potential application to patients is extremely exciting as it may provide a novel and clinically practical method to overcome low cell survival in cell-based therapy," Chan said. "We are currently exploring other beneficial properties of the reprogrammed MSCs for other therapeutic applications."

"Many investigators have speculated that differentiation should improve the utility of stem cells for transplantation, but how far to differentiate the cells for the best outcome is a difficult question. Dr Chan's team have helped provide an answer by educating mesenchymal stem cells by pre-differentiating to the desired lineage before de-differentiation, making MSCs easier to manipulate and implant," said Dr. Mark Pittenger. "Interesting questions still remain for future work such as which factors are expressed in the pre-differentiated stem cells that persist upon de-differentiation and can the de-differcetiated cells be frozen for future use?"

Citation: "Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential;" Yang Liu, Hsiao Chang Chan et al.; Stem Cells, published online 3 November 2011 ahead of print, DOI: 10.1002/stcm.764

Abstract:

http://dx.doi.org/10.1002/stem.764

Contact: Hsiao Chang Chan, hsiaocchan@cuhk .edu.hk
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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Lab World
Date:Nov 21, 2011
Words:534
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