Leukemia Inhibitory Factor increases survival of pluripotent stem cell-derived cardiomyocytes

BLUGUERMANN CAROLINA; ROMORINI LEONARDO; DENIS EVSEENKO; GARATE XIMENA; NEIMAN GABRIEL; SEVLEVER GUSTAVO EMILIO; SCASSA MARÍA ELIDA; MIRIUKA SANTIAGO GABRIEL

Journal of Cardiovascular Traslational Research

Springer Science

Año: 2017

1937-5387

Leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) family ofcytokines, is a growth and differentiation factor with pleiotropic biological functions. Ithas been reported that LIF acts at different stages during mesoderm developmentincluding the specification of the hematopoietic and endothelial cells and thedevelopment of the cardiovascular system. Also, it has been shown that LIF has acytoprotective effect on neonatal murine cardiomyocytes (CMs) in culture, but little isknown about the presence and role of LIF during human cardiogenesis. Thus, weanalyzed the effects of LIF on human pluripotent stem cells (PSCs) undergoing cardiacdifferentiation. We first showed that LIF is expressed in the human heart during earlydevelopment. We found that the addition of LIF within a precise time window during thein vitro differentiation process significantly increased CMs viability. This finding wasassociated to a decrease in the expression of pro-apoptotic protein Bax, which coincideswith a reduction of the apoptotic rate. Therefore, the addition of LIF may represent apromising strategy for increasing CMs survival and in consequence an important way toimprove the differentiation of cardiac cells from PSCs.