Therapeutic benefits of CD90-negative cardiac stromal cells in rats with a 30-day chronic infarct

Deliang Shen; Miaoda Shen; Hongxia Liang; Junnan Tang; Bo Wang; Chuang Liu; Peiwen Wang; Jianzeng Dong; Ling Li; Jinying Zhang; Thomas G Caranasos

doi:10.1111/jcmm.13517

Therapeutic benefits of CD90-negative cardiac stromal cells in rats with a 30-day chronic infarct

J Cell Mol Med. 2018 Mar;22(3):1984-1991. doi: 10.1111/jcmm.13517. Epub 2018 Jan 17.

Authors

Deliang Shen¹, Miaoda Shen², Hongxia Liang³, Junnan Tang¹, Bo Wang¹, Chuang Liu¹, Peiwen Wang¹, Jianzeng Dong^{1

4}, Ling Li¹, Jinying Zhang¹, Thomas G Caranasos⁵

Affiliations

¹ Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
² Department of Orthopedic Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
³ Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
⁴ Department of Cardiology, Beijing Anzhen Hospital of Capital Medical University, Beijing, China.
⁵ Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

Cardiac stromal cells (CSCs) can be derived from explant cultures, and a subgroup of these cells is viewed as cardiac mesenchymal stem cells due to their expression of CD90. Here, we sought to determine the therapeutic potential of CD90-positive and CD90-negative CSCs in a rat model of chronic myocardial infarction. We obtain CD90-positive and CD90-negative fractions of CSCs from rat myocardial tissue explant cultures by magnetically activated cell sorting. In vitro, CD90-negative CSCs outperform CD90-positive CSCs in tube formation and cardiomyocyte functional assays. In rats with a 30-day infarct, injection of CD90-negative CSCs augments cardiac function in the infarct in a way superior to that from CD90-positive CSCs and unsorted CSCs. Histological analysis revealed that CD90-negative CSCs increase vascularization in the infarct. Our results suggest that CD90-negative CSCs could be a development candidate as a new cell therapy product for chronic myocardial infarction.

Keywords: CD90; cardiac regeneration; myocardial infarction; stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism
Disease Models, Animal
Fibroblast Growth Factors / genetics
Fibroblast Growth Factors / metabolism
Gene Expression
Gene Expression Profiling
Hepatocyte Growth Factor / genetics
Hepatocyte Growth Factor / metabolism
Human Umbilical Vein Endothelial Cells / cytology
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Immunomagnetic Separation
Ki-67 Antigen / genetics
Ki-67 Antigen / metabolism
Male
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / metabolism
Myocardial Infarction / genetics
Myocardial Infarction / metabolism
Myocardial Infarction / pathology
Myocardial Infarction / therapy*
Myocardium / metabolism
Myocardium / pathology
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / pathology
Neovascularization, Physiologic
Primary Cell Culture
Rats
Rats, Sprague-Dawley
Thy-1 Antigens / deficiency
Thy-1 Antigens / genetics*
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism

Substances

Biomarkers
HGF protein, human
Ki-67 Antigen
Thy-1 Antigens
Vascular Endothelial Growth Factor A
vascular endothelial growth factor A, rat
fibroblast growth factor 13
Fibroblast Growth Factors
Hepatocyte Growth Factor