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

CASTILLO MARTHA GIOVANNA; GIMENO ML; GIMÉNEZ, CARLOS SEBASTIÁN; BAUZÁ MARÍA DEL ROSARIO; LÓPEZ AYELÉN EMILCE; LOCATELLI PAOLA; PERONE MARCELO; OLEA FERNANDA DANIELA; CROTTOGINI ALBERTO; CUNIBERTI LUIS

Mar del Plata

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2018

SAIC-SAFIS

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 mobilized into the peripheral blood in patients with acute myocardial infarction (AMI). In addition, the therapeutic efficiency of xenotransplanting hMuse in non-immunosuppressed rabbits with AMI was recently demonstrated. However, this novel approach has not been tested 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 capacity of differentiation into myocardiocytes, in sheep with AMI. Methods. Under ethical approval and written informed consent, hMuse were isolated from abdominal lipoaspirates using severe cellular stress procedure. hMuse were stained with PKH26 Red Fluorescent Dye for in vivo tracking. Ten million pre-stained hMuse were delivered in 10 intramyocardial injections in the peri-infarct zone (hMuse group, n=4). Additional sheep received PBS (Placebo, n=4). One week later, animals were sacrificed, hMuse were tracked, and capillary and arteriolar densities were measured in representative myocardial samples (immunohistochemistry). Results: Confocal microscopy revealed the presence of fluorescent cells in hMuse group, located mainly in the infarct border. Arteriolar density was higher in hMuse group than placebo (21.3±2.1 vs. 10.4±1 arterioles/mm2, p