title: Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Mao
authors.affiliation: Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.|The Institute of Metabolic Diseases, Qingdao University, Qingdao, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Pediatrics, Qingdao Women and Children's Hospital, 6 Tongfu Rd, Qingdao, 266011, China.
authors.forename: Benzhen
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Chi
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China.
authors.forename: Caining
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, the Affiliated Hospital of Qingdao University, 16 Jiangsu Rd, Qingdao, 266003, China. zipuli2016@sina.com.|Department of Pediatrics, Qingdao Women and Children's Hospital, 6 Tongfu Rd, Qingdao, 266011, China. zipuli2016@sina.com.
authors.forename: Zipu
authors.identifier: 0000-0002-5244-272X
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000097:blood / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013318:Stroke Volume / Q000502:physiology*; D014183:Transplantation, Heterologous; D019210:Troponin I / Q000097:blood / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D053605:Leukemia Inhibitory Factor; D019210:Troponin I; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020097:Natriuretic Peptide, Brain; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Cardiac function; Dilated cardiomyopathy (DCM); Intramuscular injection; Mesenchymal stem cells (MSCs); Paracrine