Stem Cell Therapy - Are We There Yet?
The potential of stem cell therapy still lies ahead. The only outcome reliably achieved to date in human medicine is the reduction of chronic inflammation via transplantation of mesenchymal stem cells. The real goal for this field is, however, the replacement and enhanced performance of specific stem cell populations in order to produce regeneration that does not normally take place, or to restore youthful tissue maintenance in the old. That remains to be achieved in anything more than a preliminary way in even the most well studied stem cell populations, those of muscle, brain, and bone marrow.
In murine models, there have been some therapeutic successes reported when aged systems have an influx of stem cells with restored or robust function. One such study showed that ex-vivo treatment of aged muscle stem cells (MuSCs) with a small-molecule inhibitor and a culturing on a porous hydrogel substrate was able to restore potential to the aged MuSCs, and the improved potential was able to impart restored muscle repair when these cells were transplanted into injured, aged muscle. Another exciting study on aged MuSC rejuvenation recently reported that transplantation of aged MuSCs pulsed with transient expression of iPSC reprogramming factors was able to repair injured muscled from aged mice at a rate similar to young MuSCs. These data were also translated in human studies where aged human MuSCs were transiently reprogrammed and transplanted back to the aged donor and showed increased new tissue formation.
On the flip side of these very positive results of improved muscle repair from reprogrammed MuSCs in the aged environment, hematopoietic stem cell (HSC) transplants into aged mice did not have such promising results. In transplants of young, robust HSCs into aged recipient mice, studies report that the aged niche, where the donor stem cells home to in the bone marrow, have negative effects on the robust stem cells populations, altering the cell-intrinsic potential of the transplanted HSCs. Thus, in aged individuals, there may be complex interactions between intrinsic stem cell alterations and the systemic alterations that both need to be addressed for more effective stem cell therapies.
Harnessing the full potential of stem cells could lead to the mitigation of most aging phenotypes but, like most things worthwhile, we need to be patient to develop the most robust effects with these therapies. It will likely require the cooperation between multiple players-whether combinations of stem cell transplants or coordination between stem cell transplants and other pharmacological interventions. However, we may be just at the beginning of understanding these complex interplays.