New research published in STEM CELLS demonstrates improvements in the survival and effectiveness of transplanted stem cells. A variety of breakthroughs have been achieved through researching differentiation. Scientists have harvested cells from one part of the body and genetically adapted them to fulfill a specialized role, however, if the implanted cells are too similar to the cells of the targeted area, they may not have the plasticity to engraft and repair the injured tissue.
Research leader Dr Hsiao Chang Chan, from the Chinese University of Hong Kong explains:
“Stem cell differentiation and transplantation has been shown to improve function in conditions including degenerative diseases and blood supply disorders. However, the survival rate of transplanted cells in patients limits their overall effectiveness, which is a barrier to clinical use.”
Dr Chan and his team wanted to overcome this problem by investigating de-differentiation, a process whereby specialized, differentiated cells are reverted back to a more primitive cell.
Researchers based their investigation on multi-potent stem cells (MSCs) that can be changed 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, i.e. those forming cartilage (chondrocytes), bone (osteocytes) and fat tissue (adipocytes).
The researchers first differentiated bone marrow MSCs towards a neuronal lineage. Then they removed the differentiation conditions to enable the cell to revert back to a form with more basic cellular characteristics. After this process researchers noted increased cell survival rates following transplants.
They discovered that de-differentiated cells were more effective in improving cognitive functions and in aiding recovery from strokes in an animal model compared with un-manipulated stem cells in living specimens and in laboratory experiments.
The study’s findings confirm that de-differentiation is a workable technique for reengineering cells to a more primitive, earlier state, however, with increased cell survival rates that increase their potential for clinical use.
Dr. Chan concludes:
“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. We are currently exploring other beneficial properties of the reprogrammed MSCs for other therapeutic applications.”
Dr Mark Pittenger, STEM CELLS Associate Editor adds:
“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 has 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. 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-differentiated cells be frozen for future use?”
Written by Petra Rattue