Myocardial homing, differentiation and angiogenic effect of human Muse cells xenotransplanted in non-immunodepressed sheep with acute myocardial infarction.

CASTILLO VELASQUEZ, MG; GIMENO, ML; GIMENEZ, CS; BAUZÁ, MR; LOPEZ, A; LOCATELLI, P; PERONE, MJ; OLEA, FD; CROTTOGINI, AJ; CUNIBERTI, L

Congreso; Reunión Conjunta de SAIC, SAI y SAFIS; 2018

Introduction. Multilineage differentiating stress-enduring (Muse)cells are non-tumorigenic endogenous pluripotent-like stem cells.Recently it was shown that human Muse cells (hMuse) were mobilizedinto the peripheral blood in patients with acute myocardialinfarction (AMI). In addition, the therapeutic efficiency of xenotransplantinghMuse in non-immunosuppressed rabbits with AMI was recentlydemonstrated. However, this novel approach has not beentested in a large mammalian model closer to the clinical setting.Thus we examined the retention of hMuse 7 days after xenotransplantation,their ability to induce angiogenesis and their capacityof differentiation into myocardiocytes, in sheep with AMI. Methods.Under ethical approval and written informed consent, hMuse wereisolated from abdominal lipoaspirates using severe cellular stressprocedure. hMuse were stained with PKH26 Red Fluorescent Dyefor in vivo tracking. Ten million pre-stained hMuse were delivered in10 intramyocardial injections in the peri-infarct zone (hMuse group,n=4). Additional sheep received PBS (Placebo, n=4). One weeklater, animals were sacrificed, hMuse were tracked, and capillaryand arteriolar densities were measured in representative myocardialsamples (immunohistochemistry). Results: Confocal microscopyrevealed the presence of fluorescent cells in hMuse group, locatedmainly in the infarct border. Arteriolar density was higher in hMusegroup than placebo (21.3±2.1 vs. 10.4±1 arterioles/mm2, p