title: Paracrine action of mesenchymal stem cells revealed by single cell gene profiling in infarcted murine hearts.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have been recently demonstrated as a promising stem cell type to rescue damaged myocardium after acute infarction. One of the most important mechanisms underlying their therapeutic effects is the secretion of paracrine factors. However, the expression profile of paracrine factors of MSCs in infarcted hearts, especially at single cell level, is poorly defined.
  
  
  RESULTS
  We aimed to depict the transcriptional profile of paracrine factors secreted by MSCs in vivo, with particular interest in the comparison between normal and infarcted hearts. Bone marrow mesenchymal stem cells were isolated and injected into mice hearts immediately after infarction surgery. Bioluminescence imaging (BLI) indicated a proportion of cells still alive even up to 10 days post surgery. Paralleled with survived cells, cardiac function was significantly improved after MSC injection compared to that in PBS-injected mice, indicated by MRI and histology. Despite increased number of vessels in MSC-injected hearts, endothelial cells and cardiomyocytes transdifferentiation were not observed in infarcted hearts 5 days after infarction. Furthermore, laser capture microdissection (LCM) followed by high through-put real time PCR was employed in our study, uncovering that the injected MSCs, compared to local cardiomyocytes, displayed elevated levels of secreted factors. To further investigate the regulation of those factors, we performed single cell analysis to dissect the gene expression profile of MSCs at single cell level in infarcted and normal hearts, respectively. Consistent with the in vivo observation, a similar regulation pattern of those factors was detected in cultured MSCs under hypoxia.
  
  
  CONCLUSIONS
  Our study, for the first time, elucidated gene expression profiles, as well as regulation of paracrine factors, of MSCs at single cell level in vivo, indicating that paracrine factors from MSCs account for the improvement of cardiac function after infarction.
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Huang
authors.affiliation: Center for Cardiovascular Biology and Atherosclerosis, Department of Internal Medicine, The University of Texas, Health Science Center at Houston, Medical School, Texas Heart Institute, Houston, TX, United States of America.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Geng
authors.affiliation: Center for Coronary Heart Disease, Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Meisheng
authors.initials: M
authors.lastname: Shang
authors.affiliation: Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Jianzeng
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, P. R. China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Ma
mesh_terms: D000185:Actinin / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D020869:Gene Expression Profiling / Q000379:methods*; D006334:Heart Function Tests; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D019899:Paracrine Communication; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D059010:Single-Cell Analysis / Q000379:methods*; D059467:Transcriptome / Q000235:genetics
chemical_list: C498529:Actn2 protein, mouse; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000185:Actinin