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

doi:10.1016/j.isci.2022.104656

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. HareSudhish Sharma, Sunjay Kaushal

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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’ secretome and immune evasion, respectively.

Original language	English
Article number	104656
Journal	iScience
Volume	25
Issue number	8
DOIs	https://doi.org/10.1016/j.isci.2022.104656
State	Published - 19 Aug 2022
Externally published	Yes

Keywords

Cell biology
Molecular biology
Molecular medicine
Stem cells research

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10.1016/j.isci.2022.104656

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Gunasekaran, M., Mishra, R., Saha, P., Morales, D., Cheng, W. C., Jayaraman, A. R., Hoffman, J. R., Davidson, L., Chen, L., Shah, A. M., Bittle, G., Fu, X., Tulshyan, A., Abdullah, M., Kingsbury, T., Civin, C., Yang, P., Davis, M. E., Bolli, R., ... Kaushal, S. (2022). Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury. iScience, 25(8), Article 104656. https://doi.org/10.1016/j.isci.2022.104656

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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 = "Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = aug,

day = "19",

doi = "10.1016/j.isci.2022.104656",

language = "English",

volume = "25",

journal = "iScience",

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Gunasekaran, M, Mishra, R, Saha, P, Morales, D, Cheng, WC, Jayaraman, AR, Hoffman, JR, Davidson, L, Chen, L, Shah, AM, Bittle, G, Fu, X, Tulshyan, A, Abdullah, M, Kingsbury, T, Civin, C, Yang, P, Davis, ME, Bolli, R, Hare, JM, Sharma, S & Kaushal, S 2022, 'Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury', iScience, vol. 25, no. 8, 104656. https://doi.org/10.1016/j.isci.2022.104656

TY - JOUR

T1 - Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury

AU - Gunasekaran, Muthukumar

AU - Mishra, Rachana

AU - Saha, Progyaparamita

AU - Morales, David

AU - Cheng, Wen Chih

AU - Jayaraman, Arun R.

AU - Hoffman, Jessica R.

AU - Davidson, Lauran

AU - Chen, Ling

AU - Shah, Aakash M.

AU - Bittle, Gregory

AU - Fu, Xuebin

AU - Tulshyan, Antariksh

AU - Abdullah, Mohamed

AU - Kingsbury, Tami

AU - Civin, Curt

AU - Yang, Peixin

AU - Davis, Michael E.

AU - Bolli, Roberto

AU - Hare, Joshua M.

AU - Sharma, Sudhish

AU - Kaushal, Sunjay

PY - 2022/8/19

Y1 - 2022/8/19

N2 - 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.

AB - 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.

KW - Cell biology

KW - Molecular biology

KW - Molecular medicine

KW - Stem cells research

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U2 - 10.1016/j.isci.2022.104656

DO - 10.1016/j.isci.2022.104656

M3 - Article

AN - SCOPUS:85133889791

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 8

M1 - 104656

ER -

Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury

Abstract

Keywords

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