PMID- 28129792 OWN - NLM STAT- MEDLINE DCOM- 20171108 LR - 20220410 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 8 IP - 1 DP - 2017 Jan 28 TI - Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. PG - 18 LID - 10.1186/s13287-017-0472-y [doi] LID - 18 AB - BACKGROUND: Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. METHODS: A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy. RESULTS: Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity. CONCLUSIONS: Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium. FAU - Mao, Chenggang AU - Mao C AD - Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China. FAU - Hou, Xu AU - Hou X AD - Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China. AD - The Institute of Metabolic Diseases, Qingdao University, Qingdao, China. FAU - Wang, Benzhen AU - Wang B AD - Department of Pediatrics, Qingdao Women and Children's Hospital, 6 Tongfu Rd, Qingdao, 266011, China. FAU - Chi, Jingwei AU - Chi J AD - Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China. FAU - Jiang, Yanjie AU - Jiang Y AD - Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China. FAU - Zhang, Caining AU - Zhang C AD - Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China. FAU - Li, Zipu AU - Li Z AUID- ORCID: 0000-0002-5244-272X AD - Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China. zipuli2016@sina.com. AD - Department of Pediatrics, Qingdao Women and Children's Hospital, 6 Tongfu Rd, Qingdao, 266011, China. zipuli2016@sina.com. LA - eng PT - Journal Article DEP - 20170128 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 0 (Leukemia Inhibitory Factor) RN - 0 (Troponin I) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (vascular endothelial growth factor A, rat) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Cardiomyopathy, Dilated/genetics/metabolism/pathology/*therapy MH - Fetal Blood/cytology/metabolism MH - Gene Expression Regulation MH - Granulocyte-Macrophage Colony-Stimulating Factor/blood/genetics MH - Hepatocyte Growth Factor/blood/genetics MH - Humans MH - Injections, Intramuscular MH - Insulin-Like Growth Factor I/genetics/metabolism MH - Leukemia Inhibitory Factor/blood/genetics MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Mitochondria, Heart/metabolism/pathology MH - Myocardium/metabolism/pathology MH - Natriuretic Peptide, Brain/blood/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function/*physiology MH - Stroke Volume/*physiology MH - Transplantation, Heterologous MH - Troponin I/blood/genetics MH - Vascular Endothelial Growth Factor A/blood/genetics MH - Ventricular Function, Left/*physiology PMC - PMC5273808 OTO - NOTNLM OT - Cardiac function OT - Dilated cardiomyopathy (DCM) OT - Intramuscular injection OT - Mesenchymal stem cells (MSCs) OT - Paracrine EDAT- 2017/01/29 06:00 MHDA- 2017/11/09 06:00 PMCR- 2017/01/28 CRDT- 2017/01/29 06:00 PHST- 2016/11/24 00:00 [received] PHST- 2017/01/06 00:00 [accepted] PHST- 2016/12/22 00:00 [revised] PHST- 2017/01/29 06:00 [entrez] PHST- 2017/01/29 06:00 [pubmed] PHST- 2017/11/09 06:00 [medline] PHST- 2017/01/28 00:00 [pmc-release] AID - 10.1186/s13287-017-0472-y [pii] AID - 472 [pii] AID - 10.1186/s13287-017-0472-y [doi] PST - epublish SO - Stem Cell Res Ther. 2017 Jan 28;8(1):18. doi: 10.1186/s13287-017-0472-y.