Human induced pluripotent stem cell-derived mesenchymal stem cell conditioned medium reduced cardiac fibrosis by 36.8% and attenuated left ventricular dysfunction compared to control in a mouse model of doxorubicin-induced cardiomyopathy.
Does iPSC-MSCs-CdM prevent doxorubicin-induced cardiomyopathy in preclinical models?
Conditioned medium from iPSC-MSCs provides superior cardioprotection against doxorubicin-induced cardiomyopathy compared to BM-MSCs, driven by paracrine factors MIF and GDF-15.
Tasa de eventos absoluta: 5.1% vs 8.1%
valor p: p=<0.01
Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel "cell-free" therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects.
Zhang et al. (Tue,) conducted a other in Doxorubicin-induced cardiomyopathy (n=95). iPSC-MSCs-CdM (human induced pluripotent stem cell-derived mesenchymal stem cells conditioned medium) vs. Phosphate-buffered saline was evaluated on Cardiac fibrosis ratio (p=<0.01). Human induced pluripotent stem cell-derived mesenchymal stem cell conditioned medium reduced cardiac fibrosis by 36.8% and attenuated left ventricular dysfunction compared to control in a mouse model of doxorubicin-induced cardiomyopathy.