Cardiac Cell Therapy for Heart Repair: Should the Cells Be Left Out?

Abstract

Cardiovascular disease (CVD) is still the leading cause of death worldwide. Coronary arteryocclusion, or myocardial infarction (MI) causes massive loss of cardiomyocytes. The ischemia areais eventually replaced by a fibrotic scar. From the mechanical dysfunctions of the scar in electronictransduction, contraction and compliance, pathological cardiac dilation and heart failure develops.Once end-stage heart failure occurs, the only option is to perform heart transplantation. The sequentialchanges are termed cardiac remodeling, and are due to the lack of endogenous regenerativeactions in the adult human heart. Regenerative medicine and biomedical engineering strategies havebeen pursued to repair the damaged heart and to restore normal cardiac function. Such strategiesinclude both cellular and acellular products, in combination with biomaterials. In addition, substantialprogress has been made to elucidate the molecular and cellular mechanisms underlying heartrepair and regeneration. In this review, we summarize and discuss current therapeutic approachesfor cardiac repair and provide a perspective on novel strategies that holding potential opportunitiesfor future research and clinical translation.

RETRACTED ARTICLE: GDF11 enhances therapeutic functions of mesenchymal stem cells for angiogenesis

“…Mesenchymal stem cells (MSCs) are one of the most used cells for treatment of cardiovascular diseases [ 3 , 4 ] because they have the advantages of immune privilege, stemness, and ease of handling relative to other cell types [ 5 , 6 ]. However, MSC-mediated angiogenic therapy has been limited by poor cell survival, especially in the hostile microenvironment of ischemic tissue [ 7 ]. Many different approaches have been attempted to improve the efficacy of MSC therapy, including gene editing [ 8 ], pretreating MSCs with various chemicals or polypeptides [ 9 , 10 ], preconditioning MSCs with physiological stimuli such as hypoxia [ 11 ], or combined with other cells including endothelial progenitor cells and endothelial cells (ECs) [ 12 ].…”

Bioengineering Technologies for Cardiac Regenerative Medicine

“…In addition, exosomes derived from MSCs were integrated into hydrogels, providing a minimally invasive delivery method through intrapericardial injection. This injectable patch revolutionized the delivery of cardiac patches, which normally needs a traumatic open-chest surgery ( Zhu and Cheng, 2021 ; Zhu et al, 2021 ).…”

Utilizing Developmentally Essential Secreted Peptides Such as Thymosin Beta-4 to Remind the Adult Organs of Their Embryonic State—New Directions in Anti-Aging Regenerative Therapies

“…The goal of regenerative therapies is to aid damaged tissues with functionally intact healthy cells of the organ. This may be achieved, for instance, by activating cell proliferation and migration of the viable intact cells, by injection, recruitment, transformation and activation of various progenitor cells, or by combination of bioengineered substances to and at the damaged scene [28][29][30][31][32][33][34][35][36][37][38]. Normally, the damaged organ "solves the problem" by special remodeling of the tissue, which, particularly in the mammalian heart, sadly results in a significant decrease of contractility and function (Figure 1).…”

“…As mentioned, an additional alternative for creating a clinical imperative to offset cardiac cell death during acute ischemic injury and to promote cardiac function is the utilization of intra-or extracardiac stem cells [24,[28][29][30][33][34][35]37,[52][53][54][55][56][57]. Although the stem cell population could maintain a balance between cell death and renewal under normal circumstances, despite its promises regarding heart failure therapy [38], it is sadly insufficient for proper repair following infarction.…”

“…Thus, introduction of extracardiac progenitors such as mesenchymal or embryonic endothelial precursors may better support functionality. This approach, however, has been deemed controversial [56,58] as the technical hurdles regarding progenitor cell delivery and differentiation have thus far prevented broad clinical applications following hypoxia [28].…”