Possible advantages of stem cell transfusion into the peripheral circulation, as opposed to localized transplantation in situ

Studies to date have overlooked the possible limitations of transplanting stem cells locally (in situ), directly at the site of tissue or organ damage. This approach is contrary to the intrinsic physiological process of tissue and organ regeneration in vivo, which is thought to involve the activation of stem cells resident within the transplanted tissues or their mobilization from ectopic sites, in particular the bone marrow. Signaling pathways and other molecular processes within stem cells transplanted in situ may not be primed to achieve optimal tissue regeneration and may even be confused by the sudden rapid transition in the cellular microenvironment encountered during transplantation. Moreover, there is a risk of the transplanted cells giving rise to undesired lineages at the transplantation site. A novel alternative would be to transfuse stem cells into the peripheral blood circulation, followed by induced homing to the site of tissue damage. This could better replicate the natural physiological process of tissue repair in vivo. Transfusion into the peripheral blood circulation could be a strategy to augment the inadequate mobilization of endogenous adult stem cells from ectopic sites for tissue repair, which may be the case for older patients. The transfused stem cells can then be induced to home in on a damaged tissue or organ, via the controlled release of specific cytokines or chemokines (i.e., stromal cell derived factor-1) emanating from that particular tissue or organ. The gradient of released cytokines/chemokines within the peripheral blood circulation would then direct the chemotactic migration and homing of the transfused stem cells to the target tissue or organ.