Transplanted human embryonic stem cells as biological 'catalysts' for tissue repair and regeneration

Abstract

Human embryonic stem cells have tremendous potential in the newly emerging field of regenerative medicine. Recently, it was demonstrated that the rescue of lethal cardiac defects in Id knockout mutant mouse embryos was not due to the transplanted cells giving rise to functional new tissues within the defective embryonic heart. Instead, there is indirect evidence that the observed therapeutic effect was due to various secreted factors emanating from the transplanted cells. This therefore, introduces the exciting prospect of utilizing human embryonic stem cells as biological 'catalysts' to promote tissue repair and regeneration in transplantation therapy. However, the immunological barrier against allogenic transplantation, as well as the teratogenic potential of human embryonic stem cells poses major technical challenges. A possible strategy to overcome the immunological barrier may be to impose a temporary regimen of immunosuppressive drugs followed by their gradual withdrawal, once adequate tissue regeneration has been achieved. Other more novel alternatives include the use of microencapsulation to block interaction with the transplant recipient's immune system, and co-transplantation with bone marrow-derived mesenchymal stem cells, which have been demonstrated to possess immuno-suppressive properties. The teratogenic potential of human embryonic stem cells could possibly be alleviated by directing the differentiation of these cells to specific lineages prior to transplantation, or through mitotic inactivation (γ irradiation or mitomycin C exposure). Co-transplantation with autologous adult stem cells may represent a novel strategy to further enhance the 'catalytic' effects of human embryonic stem cells. The various factors secreted by human embryonic stem cells could then have a concentrated localized effect on relatively large numbers of co-transplanted autologous adult stem cells, which may in turn lead to enhanced repair and regeneration of the damaged tissue or organ. Moreover, there is also a possibility that synergistic interactions between the co-transplanted human embryonic stem cells and autologous adult stem cells, may somehow produce signals for the recruitment and migration of additional endogenous adult stem cells within the recipient (i.e. peripheral blood circulation, bone marrow), which could further enhance organ/tissue regeneration. Hence, the potential use of human embryonic stem cells as biological 'catalysts' to stimulate tissue repair and regeneration, appears to hold tremendous promise in the field of regenerative medicine. This new therapeutic strategy needs to thoroughly investigated, in view of its potentially important clinical applications. © 2004 Elsevier Ltd. All rights reserved.