Mesenchymal stem cell: present challenges and prospective cellular cardiomyoplasty approaches for myocardial regeneration.
Myocardial ischemia and cardiac dysfunction have been known to follow ischemic heart diseases (IHDs). Despite a plethora of conventional treatment options, their efficacies are associated with skepticism. Cell therapies harbor a promising potential for vascular and cardiac repair, which is corroborated by adequate preclinical evidence. The underlying objectives behind cardiac regenerative therapies subsume enhancing angiomyogenesis in the ischemic myocardium, ameliorating cellular apoptosis, regenerating the damaged myocardium, repopulating the lost resident myocardial cells (smooth muscle, cardiomyocyte, and endothelial cells), and finally, decreasing fibrosis with a consequent reduction in ventricular remodeling. Although-cell based cardiomyoplasty approaches have an immense potential, their clinical utilization is limited owing to the increased need for better candidates for cellular cardiomyoplasty, better routes of delivery, appropriate dose for efficient engraftment, and better preconditioning or genetic-modification strategies for the progenitor and stem cells. Mesenchymal stem cells (MSCs) have emerged as powerful candidates in mediating myocardial repair owing to their unique properties of multipotency, transdifferentiation, intercellular connection with the resident cardiomyocytes via connexin 43 (Cx43)-positive gap junctions in the myocardium, and most important, immunomodulation. In this review, we present an in-depth discussion on the complexities associated with stem and progenitor cell therapies, the potential of preclinical approaches involving MSCs for myocardial repair, and an account of the past milestones and ongoing MSC-based trials in humans.
Paul
Debayon
D
Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030-1110, USA.
Samuel
Samson Mathews
SM
Maulik
Nilanjana
N
D000818:Animals; D002454:Cell Differentiation; D017690:Cell Transplantation; D005260:Female; D006321:Heart / Q000503:physiopathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration