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Combined Transplantation of Human MSCs and ECFCs Improves Cardiac Function and Decrease Cardiomyocyte Apoptosis After Acute Myocardial Infarction

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Abstract

Background

Ischemic heart disease, often caused by an acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. Despite significant advances in medical and procedural therapies, millions of AMI patients progress to develop heart failure every year.

Methods

Here, we examine the combination therapy of human mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) to reduce the early ischemic damage (MSCs) and enhance angiogenesis (ECFCs) in a pre-clinical model of acute myocardial infarction. NOD/SCID mice were subjected to AMI followed by transplantation of MSCs and ECFCs either alone or in combination. Cardiomyocyte apoptosis and cardiac functional recovery were assessed in short- and long-term follow-up studies.

Results

At 1 day after AMI, MSC- and ECFC-treated animals demonstrated significantly lower cardiomyocyte apoptosis compared to vehicle-treated animals. This phenomenon was associated with a significant reduction in infarct size, cardiac fibrosis, and improvement in functional cardiac recovery 4 weeks after AMI.

Conclusions

The use of ECFCs, MSCs, and the combination of both cell types reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of AMI. These results support the use of this combined cell therapy approach in future human studies during the acute phase of ischemic cardiac injury.

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Fig. 1

Data Availability

Data is available upon request submitted to the corresponding author.

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Acknowledgements

Dr. Abdel-Latif is supported by the NIH Grant R01 HL124266.

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Authors and Affiliations

  1. Gill Heart and Vascular Institute and Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY, USA

    Himi Tripathi, Renee Donahue, Bryana Levitan & Ahmed Abdel-Latif

  2. Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    Alison Domingues & Mariusz Z. Ratajczak

  3. Université de Paris, INSERM, Innovative Therapies in Haemostasis, 75006, Paris, France

    Alison Domingues, Audrey Cras, Coralie L. Guerin & David M. Smadja

  4. Cell Therapy Department, AP-HP, Hôpital Saint Louis, 75010, Paris, France

    Audrey Cras

  5. Curie Institute, Paris, France

    Coralie L. Guerin

  6. The Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Erhe Gao

  7. Hematology Department and Biosurgical Research Lab (Carpentier Foundation), AP-HP, Hôpital Européen Georges Pompidou, 75015, Paris, France

    David M. Smadja

  8. Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, MI, USA

    Ahmed Abdel-Latif

  9. Division of Cardiovascular Medicine, University of Michigan and the Ann Arbor VA Medical Center, Ann Arbor, MI, USA

    Ahmed Abdel-Latif

  10. Canadian Cardiac Research Center, Department of Internal Medicine, Division of Cardiology, University of Saskatchewan, Saskatoon, SK, Canada

    Wadea M. Tarhuni

Authors
  1. Himi Tripathi
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  2. Alison Domingues
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  3. Renee Donahue
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  4. Audrey Cras
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  5. Coralie L. Guerin
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  6. Erhe Gao
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  7. Bryana Levitan
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  8. Mariusz Z. Ratajczak
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  9. David M. Smadja
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  10. Ahmed Abdel-Latif
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  11. Wadea M. Tarhuni
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Corresponding author

Correspondence to Ahmed Abdel-Latif.

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Tripathi, H., Domingues, A., Donahue, R. et al. Combined Transplantation of Human MSCs and ECFCs Improves Cardiac Function and Decrease Cardiomyocyte Apoptosis After Acute Myocardial Infarction. Stem Cell Rev and Rep 19, 573–577 (2023). https://doi.org/10.1007/s12015-022-10468-z

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  • DOI: https://doi.org/10.1007/s12015-022-10468-z

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