[Improvement of musculoskeletal function by cell-based therapy using mesenchymal stem cells with a prolonged life...

Cell transplantation has recently been attempted to improve musculoskeletal function. Many types of cells, such as embryonic stem cells, fetal cardiomyocytes, myoblasts, bone marrow hematopoietic cells, and mesenchymal stem cells (MSCs), have been transplanted to functionally restore damaged or diseased tissue in animal models, and marrow-derived mononuclear cells have been injected into ischemic limb clinically. MSCs can be a useful source of cell transplantation for several reasons:they have the ability to proliferate and differentiate into mesodermal tissues, including myocytes, they entail no ethical or immunological problems, and bone marrow aspiration is an established routine procedure. When placed in appropriate in vitro and in vivo environments, MSCs can give rise to all major mesenchymal tissues, such as bone, cartilage, muscle, and adipose tissue. Direct injection of murine and porcine MSCs into skeletal muscles has been shown to be feasible in murine models of ischemic limb. Large numbers of cells must be injected into damaged sites in ischemic limb to restore muscular function in humans, and cells need to be injected into the entire limb. Until now, however, there have been no reports of a sufficient number of differentiated human myocytes ever having been obtained to restore muscular function of ischemic limb. One of the reasons for this is that the life span of human cells in vitro is limited. Human cells reach senescence or stop cell growth after a limited number of cell replications, and the average number of hMSC population doublings (PDs) has been found to be 38, implying that it would be difficult to obtain enough cells to restore the function of ischemic limb. To resolve these problems and to establish a model of cell-based therapy, prolongation of the life span of hMSCs without affecting differentiation capability is essential.