iScience (Aug 2022)
Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury
- Muthukumar Gunasekaran,
- Rachana Mishra,
- Progyaparamita Saha,
- David Morales,
- Wen-Chih Cheng,
- Arun R. Jayaraman,
- Jessica R. Hoffman,
- Lauran Davidson,
- Ling Chen,
- Aakash M. Shah,
- Gregory Bittle,
- Xuebin Fu,
- Antariksh Tulshyan,
- Mohamed Abdullah,
- Tami Kingsbury,
- Curt Civin,
- Peixin Yang,
- Michael E. Davis,
- Roberto Bolli,
- Joshua M. Hare,
- Sudhish Sharma,
- Sunjay Kaushal
Affiliations
- Muthukumar Gunasekaran
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Rachana Mishra
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Progyaparamita Saha
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- David Morales
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Wen-Chih Cheng
- Center for Stem Cell Biology and Regenerative Medicine, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Arun R. Jayaraman
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, W200, Atlanta, GA 30322, USA
- Jessica R. Hoffman
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, W200, Atlanta, GA 30322, USA
- Lauran Davidson
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Ling Chen
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Aakash M. Shah
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Gregory Bittle
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Xuebin Fu
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Antariksh Tulshyan
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Mohamed Abdullah
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA; Department of Cardiothoracic Surgery, Cairo University, Cairo 11553, Egypt
- Tami Kingsbury
- Center for Stem Cell Biology and Regenerative Medicine, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Curt Civin
- Center for Stem Cell Biology and Regenerative Medicine, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Peixin Yang
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA
- Michael E. Davis
- Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive, W200, Atlanta, GA 30322, USA
- Roberto Bolli
- Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40202, USA
- Joshua M. Hare
- University of Miami, Miller School of Medicine, Miami, FL, USA
- Sudhish Sharma
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA; Corresponding author
- Sunjay Kaushal
- Departments of Surgery and Pediatrics, Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Chicago, IL 60611, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 8
p. 104656
Abstract
Summary: Successful cell therapy requires cells to resist the hostile ischemic myocardium, be retained to continue secreting cardioprotective growth factors/exosomes, and resist immunological host responses. Clinically relevant stem/progenitor cells in a rodent model of acute myocardial infarction (MI) demonstrated that neonatal cardiac mesenchymal stromal cells (nMSCs) provide the most robust cardiac functional recovery. Transplanted nMSCs significantly increased the number of tissue reparative macrophages and regulatory T-cells and decreased monocyte-derived inflammatory macrophages and neutrophils in the host myocardium. mRNA microarray and single-cell analyses combined with targeted depletion studies established CD47 in nMSCs as a key molecule responsible for cell retention in the myocardium through an antiphagocytic mechanism regulated by miR34a-5p. Gain and loss-of-function studies demonstrated that miR34a-5p also regulated the production of exosomes and cardioprotective paracrine factors in the nMSC secretome. In conclusion, miR34a-5p and CD47 play an important role in determining the composition of nMSCs’ secretome and immune evasion, respectively.
