H2O2 resistant mesoangioblast clone isolation with a distinct survival advantage in vitro and in vivo

Abstract

The release of molecules from damaged tissues stimulates both resident and circulating stem cells to initiate a tissue repair programme. 1 However, during transplantation procedures the therapeutic efficacy of stem cells is compromised by reduced homing capability towards the target site.2,3 Furthermore, cell survival is very low and many studies focused on improving cell viability upon implantation. In this study, we performed in vitrosevere oxidative stress to select some more resistant mouse mesoangioblasts, vessel-associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. We found that the selected subpopulation retains selfrenewal and myogenic differentiation capabilities under physiological growth conditions, showing, also, an enhancement in cell survival and migration capabilities under stress conditions respect to the unselected cells. In fact, following oxidative stress treatment the isolated cell subpopulation showed more resistance, survival and recovery properties. To evaluate whether or not the isolated cell clone showed selective advantages over the parental mesoangioblasts, we carried out in vivo experiments using immunocompromised dystrophic mice. We injected intramuscularly the Tibialis Anterior with both the selected cells and the parental cells. Actually resistant mesoangioblasts displayed markedly enhanced survival and integration capabilities into the host damaged skeletal muscle, displaying more than 70% increase in integration compared to the non-selected mesoangioblast cell population. In conclusion, the positive effects of sorting on mesoangioblast cells suggest that a selection step using oxidative stress preconditioning may provide a novel methodology to select for resistant cells that can be used in regenerative tissue applications to prevent high mortality rates upon transplantation.