Samuel J White1, James J H Chong2. 1. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia. 2. Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia; Department of Cardiology, Westmead Hospital, Westmead, New South Wales, Australia. Electronic address: james.Chong@sydney.edu.au.
Abstract
PURPOSE: Cardiac pathologies remain a dominant cause of morbidity and mortality within the community. The drive to develop therapies capable of repairing damaged heart tissue to achieve clinically significant restoration of function has motivated the pursuit of novel approaches such as cell therapy. To this end, evidence of therapeutic benefits achieved by using mesenchymal stem cells (MSCs) has captured considerable interest despite a relative lack of information regarding the mechanisms involved. This narrative review synthesizes and interprets the current literature describing mechanisms by which MSCs can elicit cardiac repair, thereby directing attention to avenues of further inquiry. METHODS: OVID versions of MEDLINE and EMBASE were searched for studies describing the role of MSCs in mammalian cardiac repair. Additional studies were sourced from the reference lists of relevant articles and other personal files. FINDINGS: MSCs elicit cardiac repair in a range of in vitro systems and animal models of diseases such as myocardial infarction and heart failure. Important mechanisms include the preservation of myocardial contractility, the promotion of angiogenesis, and the modulation of fibrosis. Exposing in vitro MSCs to a microenvironment reflective of that encountered in the injured heart seems to potentiate these therapeutic mechanisms. IMPLICATIONS: Promising results in animal studies warrant continuation of clinical MSC cardiac therapy studies. Paracrine functions of MSCs seem to be the dominant mechanism of cardiac repair over direct cellular effects. Although integral, the MSC secretome remains poorly defined. In addition, most of the mechanistic data within the literature have been derived from animal MSC research, necessitating more human MSC-based work.
PURPOSE: Cardiac pathologies remain a dominant cause of morbidity and mortality within the community. The drive to develop therapies capable of repairing damaged heart tissue to achieve clinically significant restoration of function has motivated the pursuit of novel approaches such as cell therapy. To this end, evidence of therapeutic benefits achieved by using mesenchymal stem cells (MSCs) has captured considerable interest despite a relative lack of information regarding the mechanisms involved. This narrative review synthesizes and interprets the current literature describing mechanisms by which MSCs can elicit cardiac repair, thereby directing attention to avenues of further inquiry. METHODS: OVID versions of MEDLINE and EMBASE were searched for studies describing the role of MSCs in mammalian cardiac repair. Additional studies were sourced from the reference lists of relevant articles and other personal files. FINDINGS: MSCs elicit cardiac repair in a range of in vitro systems and animal models of diseases such as myocardial infarction and heart failure. Important mechanisms include the preservation of myocardial contractility, the promotion of angiogenesis, and the modulation of fibrosis. Exposing in vitro MSCs to a microenvironment reflective of that encountered in the injured heart seems to potentiate these therapeutic mechanisms. IMPLICATIONS: Promising results in animal studies warrant continuation of clinical MSC cardiac therapy studies. Paracrine functions of MSCs seem to be the dominant mechanism of cardiac repair over direct cellular effects. Although integral, the MSC secretome remains poorly defined. In addition, most of the mechanistic data within the literature have been derived from animal MSC research, necessitating more human MSC-based work.
Authors: Darrian Bugg; Logan R J Bailey; Ross C Bretherton; Kylie E Beach; Isabella M Reichardt; Kalen Z Robeson; Anna C Reese; Jagadambika Gunaje; Galina Flint; Cole A DeForest; April Stempien-Otero; Jennifer Davis Journal: Cell Stem Cell Date: 2022-02-16 Impact factor: 25.269