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

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Abstract

The release of molecules from damaged tissues stimulates bothresident and circulating stem cells to initiate a tissue repair programme.1 However, during transplantation procedures the therapeuticefficacy of stem cells is compromised by reduced homingcapability towards the target site.2,3 Furthermore, cell survivalis very low and many studies focused on improving cell viabilityupon implantation. In this study, we performed in vitrosevere oxidative stress to select some more resistant mousemesoangioblasts, vessel-associated progenitor stem cellsendowed with the ability of multipotent mesoderm differentiation.We found that the selected subpopulation retains selfrenewaland myogenic differentiation capabilities under physiologicalgrowth conditions, showing, also, an enhancement in cellsurvival and migration capabilities under stress conditionsrespect to the unselected cells. In fact, following oxidative stresstreatment the isolated cell subpopulation showed more resistance,survival and recovery properties. To evaluate whether ornot the isolated cell clone showed selective advantages over theparental mesoangioblasts, we carried out in vivo experimentsusing immunocompromised dystrophic mice. We injected intramuscularlythe Tibialis Anterior with both the selected cells andthe parental cells. Actually resistant mesoangioblasts displayedmarkedly enhanced survival and integration capabilities into thehost damaged skeletal muscle, displaying more than 70%increase in integration compared to the non-selected mesoangioblastcell population. In conclusion, the positive effects ofsorting on mesoangioblast cells suggest that a selection stepusing oxidative stress preconditioning may provide a novelmethodology to select for resistant cells that can be used inregenerative tissue applications to prevent high mortality ratesupon transplantation.
Original languageEnglish
Pages (from-to)31-32
Number of pages2
JournalEUROPEAN JOURNAL OF HISTOCHEMISTRY
Volume61/supplement 1
Publication statusPublished - 2017

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