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World J Stem Cells. Jan 26, 2022; 14(1): 1-40
Published online Jan 26, 2022. doi: 10.4252/wjsc.v14.i1.1
Cardiac stem cells: Current knowledge and future prospects
Radwa A Mehanna, Marwa M Essawy, Mona A Barkat, Ashraf K Awaad, Eman H Thabet, Heba A Hamed, Hagar Elkafrawy, Nehal A Khalil, Abeer Sallam, Marwa A Kholief, Samar S Ibrahim, Ghada M Mourad
Radwa A Mehanna, Eman H Thabet, Abeer Sallam, Medical Physiology Department/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Marwa M Essawy, Oral Pathology Department, Faculty of Dentistry/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Mona A Barkat, Human Anatomy and Embryology Department/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Ashraf K Awaad, Samar S Ibrahim, Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Heba A Hamed, Ghada M Mourad, Histology and Cell Biology Department/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Hagar Elkafrawy, Nehal A Khalil, Medical Biochemistry Department/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Marwa A Kholief, Forensic Medicine and Clinical toxicology Department/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Alexandria 21500, Egypt
Author contributions: Mehanna RA designed, supervised and revised the manuscript, collected and analyzed the data, and shared in figures’ creation; Mourad GM supervised the work and revised the paper; all other authors contributed to data collection, writing the manuscript, and creating figures and tables.
Supported by Science and Technology Development Fund, No. 28932; and Cardiovascular Research, Education, Prevention Foundation, CVREP - Dr. Wael Al Mahmeed Grant.
Conflict-of-interest statement: Dr. Mehanna has nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Radwa A Mehanna, MD, PhD, Academic Research, Professor, Executive President, Medical Physiology Department/Center of Excellence for Research in Regenerative Medicine and Applications, Faculty of Medicine, Alexandria University, Al Khartoum Square, Azareeta, Alexandria 21500, Egypt. radwa.mehanna@alexmed.edu.eg
Received: February 26, 2021
Peer-review started: February 26, 2021
First decision: June 24, 2021
Revised: July 2, 2021
Accepted: January 6, 2022
Article in press: January 6, 2022
Published online: January 26, 2022
Processing time: 328 Days and 4.2 Hours
Abstract

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs. Since the inception of the field several decades ago, regenerative medicine therapies, namely stem cells, have received significant attention in preclinical studies and clinical trials. Apart from their known potential for differentiation into the various body cells, stem cells enhance the organ's intrinsic regenerative capacity by altering its environment, whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration. Recently, research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells (CSCs/CPCs). The global burden of cardiovascular diseases’ morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy. This review will discuss the nature of each of the CSCs/CPCs, their environment, their interplay with other cells, and their metabolism. In addition, important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells. Moreover, the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration. Finally, the novel role of nanotechnology in cardiac regeneration will be explored.

Keywords: Cardiac stem and progenitor cells; Cardiac stem cells’ secretome; Cardiac stem cells’ niche and metabolism; Nanotechnology; Clinical trials; Combined therapy

Core Tip: With the growing evidence for the existence of regenerating cardiac stem and progenitor cells, studies to evaluate their therapeutic potential have received increasing attention. Although pre-clinical research and clinical trials have demonstrated promising results, yet the latter were often inconsistent in many aspects thus imposing the need for deeper exploration of the molecular biology and relevant pathways regulating cardiogenesis and cardiac muscle repair. This review gives an insight into cardiac stem and progenitor cells regarding their embryological origin, populations, niche, secretome, and metabolism. It overviews the current preclinical research, including medical nanotechnology, and the clinical trials generally applied for cardiac regeneration.