biostudies-literatureZhang YHKU State Key Laboratory of Pharmaceutical BiotechnologyHKUScience and Technology Foundation of Guangdong ProvinceNational Natural Science Foundation of ChinaTheme-based Research Scheme749-763https://www.ebi.ac.uk/biostudies/studies/S-EPMC5063626biostudies-literatureUnknown7(4)Mesenchymal stem cells (MSCs) can donate mitochondria and rescue anthracycline-induced cardiomyocyte (CM) damage, although the underlying mechanisms remain elusive. We determined that the superior efficiency of mitochondrial transfer by human induced-pluripotent-stem-cell-derived MSCs (iPSC-MSCs) compared with bone marrow-derived MSCs (BM-MSCs) is due to high expression of intrinsic Rho GTPase 1 (MIRO1). Further, due to a higher level of TNFαIP2 expression, iPSC-MSCs are more responsive to tumor necrosis factor alpha (TNF-α)-induced tunneling nanotube (TNT) formation for mitochondrial transfer to CMs, which is regulated via the TNF-α/NF-κB/TNFαIP2 signaling pathway. Inhibition of TNFαIP2 or MIRO1 in iPSC-MSCs reduced the efficiency of mitochondrial transfer and decreased CMs protection. CoStem cell reportsiPSC-MSCs with High Intrinsic MIRO1 and Sensitivity to TNF-α Yield Efficacious Mitochondrial Transfer to Rescue Anthracycline-Induced Cardiomyopathy.PMC506362631270967201007176100T12-705/11315714072014091762212015B020225001Chai YHTse HFChow YLiang XLiang YHan SLi XZhang ZZhang YXu AJiang DLiao SYu ZYue WLian QChiu SMfalseiPSC-MSCs with High Intrinsic MIRO1 and Sensitivity to TNF-α Yield Efficacious Mitochondrial Transfer to Rescue Anthracycline-Induced Cardiomyopathy.Mesenchymal stem cells (MSCs) can donate mitochondria and rescue anthracycline-induced cardiomyocyte (CM) damage, although the underlying mechanisms remain elusive. We determined that the superior efficiency of mitochondrial transfer by human induced-pluripotent-stem-cell-derived MSCs (iPSC-MSCs) compared with bone marrow-derived MSCs (BM-MSCs) is due to high expression of intrinsic Rho GTPase 1 (MIRO1). Further, due to a higher level of TNFαIP2 expression, iPSC-MSCs are more responsive to tumor necrosis factor alpha (TNF-α)-induced tunneling nanotube (TNT) formation for mitochondrial transfer to CMs, which is regulated via the TNF-α/NF-κB/TNFαIP2 signaling pathway. Inhibition of TNFαIP2 or MIRO1 in iPSC-MSCs reduced the efficiency of mitochondrial transfer and decreased CMs protection. Co2016-01-01T00:00:00Z2016 Oct2026-05-05T05:44:40.11Z2026-04-07T21:30:53.004ZS-EPMC50636262764165010.1016/j.stemcr.2016.08.009