Terminal differentiation is not a major determinant for the success of stem cell therapy - cross-talk between muscle-derived stem cells and host cells

Our research group has isolated, by a modified preplate technique [1,2], a population of muscle-derived stem cells (MDSCs) from murine post-natal skeletal muscle. These MDSCs were shown to have the ability to proliferate in vivo for an extended period of time and the capacity to self-renew, and to undergo multilineage differentiation in vitro and in vivo [2]. Current knowledge on the utility of MDSCs for enhancing repair in various musculoskeletal tissues and injured cardiac muscle and the potential for their use in clinical applications is reviewed in several publications [3-5]. Our data show that these cells display a high transplantation capacity in skeletal muscle and exhibit only limited degrees of engraftment capacity in cardiac, bone, cartilage, and nerve tissues in respective animal model injuries. Their success in repairing damaged tissues is attributed, at least in part, to their resistance to stress and through the paracrine effect that they impart on host tissues. These paracrine effects can stimulate the mobilization of host progenitor cells, stimulate the production of new blood vessels via neoangiogenesis, and possibly modulate the host immune response.The term paracrine mechanism, used herein, refers to effects that are not necessarily limited to the injury site but occur throughout the organism. In this review, we focus on studies involving MDSCs in enhancing repair and improving function in injured heart muscle and promoting repair of osteochondral defects in articular cartilage (AC), and explore the possibility that the repair is induced by host cell recruitment, angiogenic and/or anti-inflammatory activities, and not necessarily restricted to the differentiation of the implanted cells in host tissue.Cellular cardiomyoplasty (CCM), cell transplantation for cardiac repair, is an alternative therapeutic approach for the treatment of congestive heart failure [6,7]. Researchers have used a wide variety of cell types for CCM, including embryonic and ne