Umbilical cord mesenchymal stem cell therapy (Sclnow Biotechnology)

Currently, no therapy is proven to effectively improve heart failure with preserved ejection fraction (HFpEF). Although stem cell therapy has demonstrated promising results in treating ischemic heart disease, the effectiveness of treating HFpEF with human umbilical cord mesenchymal stem cells (hucMSCs) remains unclear. To answer this question, we administered hucMSCs intravenously (i.v.), either once or repetitively, in a mouse model of HFpEF induced by a high-fat diet and NG-nitroarginine methyl ester hydrochloride. hucMSC treatment improved left ventricular diastolic dysfunction, reduced heart weight and pulmonary edema, and attenuated cardiac modeling (inflammation, interstitial fibrosis, and hypertrophy) in HFpEF mice. Repeat hucMSC administration had better outcomes than a single injection. In vitro, hucMSC culture supernatants reduced maladaptive remodeling in neonatal-rat cardiomyocytes. Ribonucleic acid sequencing and protein level analysis of left ventricle (LV) tissues suggested that hucMSCs activated the protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway to treat HFpEF. Inhibition of this pathway reversed the efficacy of hucMSC treatment. In conclusion, these findings indicated that hucMSCs could be a viable therapeutic option for HFpEF.

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) have the ability to treat cardiovascular diseases (CVDs). We explored their mechanism on pyroptosis modulation in cardiac microvascular endothelial cells (CMECs).Exosomes were extracted from hUCMSCs using a differential high-speed centrifugation method, and then identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Later, the CMECs were induced by hypoxia/reoxygenation (H/R) in vitro and processed with hUCMSC-Exos or the NLRP3 inflammasome inhibitor CY-09 and the NLRP3 inflammasome activator Nigerian sodium sulfate (NSS). A rat model of ischemia/reperfusion (I/R) injury was established in vivo, followed by hUCMSC-Exo injection. Cell viability and death, and myocardial injury were assessed by CCK-8 and LDH assays and H&E staining. Levels of GSDMD-N, NLRP3, cleaved Caspase-1, IL-1β and IL-18 proteins, and inflammatory factors (IL-1β, IL-18) were determined by Western blot analysis and ELISA.H/R-induced CMECs represented attenuated cell viability and increased cell death, as well as up-regulated levels of pyroptosis proteins (cleaved Caspase-1, GSDMD-N, IL-18, IL-1β), inflammasome key protein (NLRP3) and cell supernatant inflammatory factors (IL-18, IL-1β), while hUCMSC-Exos amplified H/R-induced CMEC viability and lowered cell death, and diminished levels of NLRP3, cleaved Caspase-1, GSDMD-N, IL-18 and IL-1β proteins, and cell supernatant inflammatory factors IL-1β and IL-18. Activating the NLRP3 inflammasome/Caspase-1 pathway partially reversed the inhibitory effect of hUCMSC-Exos on CMEC pyroptosis. hUCMSC-Exos alleviated myocardial injury in I/R rats by modulating the NLRP3 inflammasome/Caspase-1 pathway.hUCMSC-Exos weakened CMEC pyroptosis by inactivating the NLRP3 inflammasome/Caspase-1 pathway.