Stem Cell Integral Membrane Transporter ABCB5 and Dermal Regeneration

PROJECT SUMMARY Project 3 will test the central hypotheses that (1) ABCB5(+) dermal mesenchymal stem cells (DMSC) are required for normal adult skin homeostasis and regeneration; (2) ABCB5(+) DMSC decline is responsible for impaired skin homeostasis and regenerative wound healing during aging; and (3) ABCB5(+) DMSC transplantation possesses therapeutic potential to restore age-related impairment of skin homeostasis and regeneration. The overall significance of this study are the potential shifts in research paradigms resulting from successful completion of this research: (1) The proposed experiments will answer a fundamental question in stem cell biology and aging that has not been addressed as-of-yet in prospective studies – To what extent is selective dysfunction in an adult stem cell compartment (vis-à-vis dysregulation of differentiated tissues) responsible for organismal aging?; and (2) Documentation of the regenerative capacity of ABCB5(+) DMSC along with demonstration of their decline as a cause age-related impairment of skin regenerative capacity will lay the foundation for targeted employment of this candidate cell therapeutic for the treatment of cutaneous wounds in aging patients.