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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00635

Mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy: Potential mechanisms, governing factors, and implications of the heart stem cell debate

  • 1Ain Shams University, Egypt
  • 2New Giza University, Egypt
  • 3Wake Forest University, United States
  • 4Al-Azhar University, Egypt
  • 5Suez Canal University, Egypt

Over the past decades, researchers have reported several mechanisms for doxorubicin (DOX)-induced cardiomyopathy, including oxidative stress, inflammation, and apoptosis. Another mechanism that has been suggested is that DOX interferes with the cell cycle and induces oxidative stress in C-kit+ cells (commonly known as cardiac progenitor cells), reducing their regenerative capacity. Cardiac regeneration through enhancing the regenerative capacity of these cells or administration of other stem cells types has been the axis of several studies over the past 20 years. Several experiments revealed that local or systemic injection with mesenchymal stem cells (MSCs) were associated with significantly improved cardiac function, ameliorated inflammatory response, and reduced myocardial fibrosis. They also showed that several factors can affect the outcome of MSCs treatment for DOX cardiomyopathy, including the MSCs type, dose, route, and timing of administration. However, there is growing evidence that the C-kit+ cells do not have a cardiac regenerative potential in the adult mammalian heart. Similarly, the protective mechanisms of MSCs against DOX-induced cardiomyopathy are not likely to include direct differentiation into cardiomyocytes and probably occur through paracrine secretion, antioxidant and anti-inflammatory effects. Better understanding of the involved mechanisms and the factors governing the outcomes of MSCs therapy is essential before moving to clinical application in patients with DOX-induced cardiomyopathy.

Keywords: Anthracyclines, cardiotoxicity, Doxorubicin, Regenerative Medicine, Stem Cells

Received: 01 Oct 2018; Accepted: 17 May 2019.

Edited by:

Emanuela Ricciotti, University of Pennsylvania, United States

Reviewed by:

Dragana Nikitovic, University of Crete, Greece
Christian Cadeddu Dessalvi, University of Cagliari, Italy  

Copyright: © 2019 Abushouk, Salem, Saad, Afify, Afifi, Afifi, Salem, Ghanem and Abdel-Daim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mohamed M. Abdel-Daim, Suez Canal University, Ismaïlia, Egypt,