Transplantation of Purified Human Skeletal Muscle-derived Pericytes Reduce Fibrosis in Injured Ischemic Muscle Tissues

FIBROSIS IN INJURED ISCHEMIC MUSCLE TISSUES Chien-Wen Chen, Masaho Okada, Kimimasa Tobita, Mihaela Crisan, Bruno Péault, Johnny Huard Department of Bioengineering, Orthopedic Surgery, Pediatrics, Stem Cell Research Center, Children’s Hospital of Pittsburgh, and McGowan Institute for Regenerative Medicine, University of Pittsburgh and UPMC and David Geffen School of Medicine, University of California at Los Angeles; [email protected] INTRODUCTION a b Vascular pericytes are the mural cells that tightly encircle capillaries and microvessels throughout the body. In general, pericytes control blood vessel maturation, stability and contractility. Multi-lineage stem/progenitor cells have been identified within virtually all organs in both human and mouse and are named diversely [1]. However, due to the retrospective discovery of these multi-lineage stem/progenitor cells in culture, the true identity of these cells in situ remained obscure. It has been hypothesized that vascular pericytes are indeed, or at least contain, stem/progenitor cells that are able to differentiate into bone, cartilage, fat tissue and odontoblasts [2]. Recently, we and others laboratories have shown that vascular pericytes purified from multiple human organs not only express classic MSC markers but harbor stem cell properties such as myo-, osteo-, chondroand adipogenic potentials [2]. Consequently, pericytes are assumed to be one of the developmental origins of MSC. Human skeletal musclederived pericytes were not only shown to regenerate skeletal muscle fibers in dystrophic as well as cardiotoxin-injured mouse muscle but also sustain impaired cardiac function after myocardial infarction in vivo [2]. Nevertheless, whether transplanted vascular pericytes contribute to the reduction of fibrosis at the site of injury remains to be elucidated. Matrix metalloproteinases (MMPs) are proteolytic enzymes responsible for extracellular matrix protein degradation with an important role in tissue remodeling processes. MMP-2 and MMP-9 activities are often implicated in fibrosis [3]. Using the animal model that has been established previously, we commenced to explore whether or not pericytes influences scar tissue formation within the damaged ischemic myocardium and attempt to elucidate the mechanism(s) of action [4].