title: The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair.
abstract: BACKGROUND
  Recent studies have demonstrated that transplantation of adipose-derived stem cell (ADSC) can improve cardiac function in animal models of myocardial infarction (MI). However, the mechanisms underlying the beneficial effect are not fully understood. In this study, we characterized the paracrine effect of transplanted ADSC and investigated its relative importance versus direct differentiation in ADSC transplantation mediated cardiac repair.
  
  
  RESULTS
  MI was experimentally induced in mice by ligation of the left anterior descending coronary artery. Either human ADSC, conditioned medium (CM) collected from the same amount of ADSC or control medium was injected into the peri-infarct region immediately after MI. Compared with the control group, both ADSC and ADSC-CM significantly reduced myocardial infarct size and improved cardiac function. The therapeutic efficacy of ADSC was moderately superior to ADSC-CM. ADSC-CM significantly reduced cardiomyocyte apoptosis in the infarct border zone, to a similar degree with ADSC treatment. ADSC enhanced angiogenesis in the infarct border zone, but to a stronger degree than that seen in the ADSC-CM treatment. ADSC was able to differentiate to endothelial cell and smooth muscle cell in post-MI heart; these ADSC-derived vascular cells amount to about 9% of the enhanced angiogenesis. No cardiomyocyte differentiated from ADSC was found.
  
  
  CONCLUSIONS
  ADSC-CM is sufficient to improve cardiac function of infarcted hearts. The therapeutic function of ADSC transplantation is mainly induced by paracrine-mediated cardioprotection and angiogenesis, while ADSC differentiation contributes a minor benefit by being involved in angiogenesis. Highlights 1 ADSC-CM is sufficient to exert a therapeutic potential. 2. ADSC was able to differentiate to vascular cells but not cardiomyocyte. 3. ADSC derived vascular cells amount to about 9% of the enhanced angiogenesis. 4. Paracrine effect is the major mechanism of ADSC therapeutic function for MI.
authors.affiliation: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Dezhong
authors.initials: D
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Liangpeng
authors.initials: L
authors.lastname: Li
authors.forename: Yulan
authors.initials: Y
authors.lastname: Peng
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Haiyun
authors.initials: H
authors.lastname: Huang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Guo
authors.forename: Xuewei
authors.initials: X
authors.lastname: Xia
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongyong
authors.initials: H
authors.lastname: Wang
authors.forename: Wei Eric
authors.initials: WE
authors.lastname: Wang
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055815:Young Adult