Direct intercellular communications dominate the interaction between adipose-derived MSCs and myofibroblasts against cardiac fibrosis.
The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treament of Infectious Diseases, Tsinghua University, Beijing, 100084, China.
Xiaokang
X
Li
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treament of Infectious Diseases, Tsinghua University, Beijing, 100084, China.|School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Hui
H
Zhao
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treament of Infectious Diseases, Tsinghua University, Beijing, 100084, China.
Chunxiao
C
Qi
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treament of Infectious Diseases, Tsinghua University, Beijing, 100084, China.
Yang
Y
Zeng
MOE Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.|Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiao Tong University, Xi'an, 710049, China.
Feng
F
Xu
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treament of Infectious Diseases, Tsinghua University, Beijing, 100084, China. duyanan@tsinghua.edu.cn.
Yanan
Y
Du
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D018920:Coculture Techniques; D005355:Fibrosis; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009206:Myocardium / Q000473:pathology*; D058628:Myofibroblasts / Q000166:cytology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley
adipose-derived mesenchymal stem cells; anti-fibrosis; cardiac fibrosis; cell-to-cell contact; myofibroblasts; stem cell therapy