Manipulation of Prenatal Stem Cell Transplant Biology

Childrens Hospital Of Philadelphia, Philadelphia PA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Duchenne's muscular dystrophy results from a genetic deletion that creates dysfunctional dystrophin protein resulting in ongoing muscle damage Injured muscle is replaced with more dysfunctional muscle from defective satellite cells which represent the muscle stem cell pool. In utero mesenchymal stem cell transplantation has been shown to result in site specific differentiation and long-term engraftment of skeletal and cardiomyocytes, however the efficiency of engraftment is very low. The rationale of this proposal is that more efficient stem cell engraftment could be obtained by manipulation of embryologic signals involved in homing and migration of myogenic progenitor cells. These signals include transcription factors, such as Pax7, which have been shown to orchestrate specification of muscle progenitors towards satellite cells and other downstream regulatory factors. My research project will involve two specific aims. Specific aim 1 will assess the molecular and biological effects of forced Pax7 expression in a defined population of multipotent adult progenitor cells (MAPC) with the focus on events involved in myogenic differentiation. The second specific aim will assess the effect of forced Pax7 expression on homing, engraftment, and differentiation of MAPC after systemic administration in a murine model of in utero stem cell transplantation.