Incorporating protein transduction domains (PTD) within intracellular proteins associated with the 'stemness' phenotype. Novel use of such recombinant 'fusion' proteins to overcome current limitations of applying autologous adult stem cells in regenerative medicine?

Abstract

Adult stem cells originating from post-natal tissues hold tremendous promise in regenerative medicine. Nevertheless, there are several deficiencies of adult stem cells that would limit their application in transplantation therapy, in particular their relative scarcity, restricted multi-potency and limited proliferative capacity in vitro. A possible approach to overcome these limitations would be to genetically modulate adult stem cells to strongly express genes that are closely associated with the 'stemness' phenotype. Overwhelming safety concerns would preclude the direct application of recombinant DNA technology in genetic modulation. Moreover, constitutive expression of 'stemness' genes would prevent adult stem cells from participating in tissue/organ regeneration upon transplantation. A novel alternative would be to incorporate protein transduction domains within intracellular proteins (i.e. transcription factors) that are associated with the 'stemness' phenotype. Such recombinant fusion proteins would then have the ability to translocate across the cell membrane and be internalized within the cytosol, thereby enabling them to exert a gene-modulatory effect on the cell, without any permanent genetic alteration. This would be particularly useful for maintaining the 'stemness' of adult stem cell populations during extensive ex vivo proliferation, to generate adequate cell numbers for transplantation therapy. © 2004 Elsevier Ltd. All rights reserved.