GDF11 enhances therapeutic efficacy of mesenchymal stem cells for myocardial infarction via YME1L-mediated OPA1 processing.
Abstract
Growth differentiation factor 11 (GDF11) has been shown to promote stem cell activity, but little is known about the effect of GDF11 on viability and therapeutic efficacy of cardiac mesenchymal stem cells (MSCs) for cardiac injury. To understand the roles of GDF11 in MSCs, mouse heart-derived MSCs were transduced with lentiviral vector carrying genes for both GDF11 and green fluorescent protein (GFP) (MSCsLV-GDF11 ) or cultured with recombinant GDF11 (MSCsrGDF11 ). Either MSCsrGDF11 or MSCs LV-GDF11 displayed less cell apoptosis and better paracrine function, as well as preserved mitochondrial morphology and function under hypoxic condition as compared with control MSCs. GDF11 enhanced phosphorylation of Smad2/3, which upregulated expression of YME1L, a mitochondria protease that balances OPA1 processing. Inhibitors of TGF-β receptor (SB431542) or Smad2/3 (SIS3) attenuated the effects of GDF11 on cell viability, mitochondrial function, and expression of YME1L. Transplantation of MSCsGDF11 into infarct heart resulted in improved cell survival and retention, leading to more angiogenesis, smaller scar size, and better cardiac function in comparison with control MSCs. GDF11 enhanced viability and therapeutic efficiency of MSCs by p...Continue Reading
References
Enhanced Cardioprotection by Human Endometrium Mesenchymal Stem Cells Driven by Exosomal MicroRNA-21
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis