@article{7ba90adef139454cb5a31f2ac750a858,
title = "Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury",
abstract = "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{\textquoteright} secretome and immune evasion, respectively.",
keywords = "Cell biology, Molecular biology, Molecular medicine, Stem cells research",
author = "Muthukumar Gunasekaran and Rachana Mishra and Progyaparamita Saha and David Morales and Cheng, {Wen Chih} and Jayaraman, {Arun R.} and Hoffman, {Jessica R.} and Lauran Davidson and Ling Chen and Shah, {Aakash M.} and Gregory Bittle and Xuebin Fu and Antariksh Tulshyan and Mohamed Abdullah and Tami Kingsbury and Curt Civin and Peixin Yang and Davis, {Michael E.} and Roberto Bolli and Hare, {Joshua M.} and Sudhish Sharma and Sunjay Kaushal",
note = "Funding Information: We acknowledge Fern P finger for assistance in preparing this manuscript. This work was supported by grants from the National Institute of Health to S.K. (HL141922, HL139060, HL145644, HL118491-06A1). M.G. (2018-MSCRFF-4326 & 2020-MSCRFD-5338) and R.M. (2018-MSCRFD-4329) were supported by the Maryland Stem Cell Research Foundation. S.S. was supported by an American Heart Association Career Development Award (18CDA34110282). J.R.H. was supported by F31HL154725 from the National Institutes of Health. M.E.D. was supported by HL145644 from the National Institutes of Health. S.K. is the founder of Neoprogen Inc. Joshua M. Hare reports having a patent for cardiac cell-based therapy and holds equity in Vestion Inc. and maintains a professional relationship with Vestion Inc. as a consultant and member of the Board of Directors and Scientific Advisory Board. Vestion Inc. did not play a role in the design, conduct, or funding of the study. Dr. Joshua Hare is the Chief Scientific Officer, a compensated consultant and board member for Longeveron Inc. and holds equity in Longeveron. Dr. Hare is also the co-inventor of intellectual property licensed to Longeveron. Longeveron did not play a role in the design, conduct, or funding of the study. The University of Miami is an equity owner in Longeveron Inc. which has licensed intellectual property from the University of Miami. S.K. R.M. and M.G. conceived the study. R.M. M.G. S.S. L.D. W.C. L.C. P.S. X.F. A.J. J.H. A.S. G.B. M.A. D.M. A.T. and T.K. performed experiments and generated all the data shown in the manuscript. S.K. P.Y. R.B. and C. C. provided theoretical assessment of the project and advice in experimental design. S.K. R.M. S.S. D.L. M.E.D. R.B. J.M.H, and M.G. interpreted the data and wrote the manuscript. The authors declare no competing interests. Funding Information: We acknowledge Fern P finger for assistance in preparing this manuscript. This work was supported by grants from the National Institute of Health to S.K. ( HL141922 , HL139060 , HL145644 , HL118491-06A1 ). M.G. ( 2018-MSCRFF-4326 & 2020-MSCRFD-5338 ) and R.M. ( 2018-MSCRFD-4329 ) were supported by the Maryland Stem Cell Research Foundation . S.S. was supported by an American Heart Association Career Development Award ( 18CDA34110282 ). J.R.H. was supported by F31HL154725 from the National Institutes of Health . M.E.D. was supported by HL145644 from the National Institutes of Health . S.K. is the founder of Neoprogen Inc. Joshua M. Hare reports having a patent for cardiac cell-based therapy and holds equity in Vestion Inc. and maintains a professional relationship with Vestion Inc. as a consultant and member of the Board of Directors and Scientific Advisory Board. Vestion Inc. did not play a role in the design, conduct, or funding of the study. Dr. Joshua Hare is the Chief Scientific Officer, a compensated consultant and board member for Longeveron Inc. and holds equity in Longeveron. Dr. Hare is also the co-inventor of intellectual property licensed to Longeveron. Longeveron did not play a role in the design, conduct, or funding of the study. The University of Miami is an equity owner in Longeveron Inc., which has licensed intellectual property from the University of Miami. Publisher Copyright: {\textcopyright} 2022",
year = "2022",
month = aug,
day = "19",
doi = "10.1016/j.isci.2022.104656",
language = "English (US)",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "8",
}