Regenerating new heart with stem cells

Abstract

This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin. IntroductionOur understanding of the process of myocardial regeneration is currently under debate. Although the adult human heart is no longer considered a static organ unable to replace its parenchymal cells during the course of life, the rate of myocyte regeneration reported thus far varies dramatically. Minimal levels of myocyte turnover, which decrease with age, have been claimed (1-5), but results have also been obtained supporting continuous myocyte renewal at a remarkable degree (6-12). Independent from the extent of the process, the debate is further intensified by contrasting views regarding the origin of newly formed cardiomyocytes (13,14). These issues have important implications because knowledge of the magnitude of cell regeneration and the mechanisms involved may offer a novel dynamic perspective of cardiac homeostasis and myocardial biology. This information is critical for the identification of strategies aiming at the restoration of the functional and structural integrity of the failing human heart.The recognition that the adult heart harbors a compartment of multipotent c-kit-positive cardiac stem cells (CSCs) (15-23) and other progenitor cell classes (24-29) capable of differentiating into cardiomyocytes and coronary vessels has raised the challenging question concerning their embryologic origin and role in cardiac cell turnover and regeneration. CSCs are stored in interstitial structures with the characteristics of stem cell niches and can divide symmetrically and asymmetrically, with the ability to self-renew and form a committed progeny (17,21,30). But whether this stem cell pool is actually self-autonomous and fully distinct from HSCs in the bone marrow remains to be determined. c-kit-positive HSCs transdifferentiate and acquire the myocyte, endothelial cell, and smooth muscle cell lineage (31), suggesting that the bone marrow participates in the homeostatic control of the myocardium and the restoration of myocytes and coronary vessels following injury. Additionally, the possibility has been advanced that postmitotic myocytes dedifferentiate, acquire an immature cell phenotype, and then reenter the cell cycle and divide (32-35), representing an alternative or complementary modality of myocyte formation. In this Review, we discuss CSCs, HS...

Comparative study of immune regulatory properties of stem cells derived from different tissues

“…Thus, two important aspects have to be discussed. First, the recognition obtained in the current study in vitro that CSCs and LSCs interfere with the inflammatory microenvironment is strongly consistent with their inherent ability to home to and divide within the damaged tissue, which has been previously demonstrated experimentally [53,73,74], in absence of inflammation in the parenchyma surrounding the integrated SCs shortly after their administration, or chronically in the regions adjacent to the regenerated myocardium, or lung structures. In other words, our data suggest that the immune modulatory properties of CSCs and LSCs here described in vitro for the first time may have a role in vivo in favoring their regenerative potential.…”

“…Because of these characteristics, therapeutically, MSCs and MSC-like SCs may have to be repeatedly employed to exert their role long-term, in absence of clear evidence of their homing and persistence inside the tissues [14][15][16][17][18][19][20]. Conversely, the delivery of tissue-specific multipotent adult SCs, such as CSCs and LSCs, to the corresponding damaged organ fails to stimulate the resident SCs nested in proximity to or distant from the injured parenchyma [73,74]. Their exclusive beneficial effect is linked to their engraftment, expansion, and ultimately the regeneration of functionally-competent cells and vessels [50,53].…”

“…In other words, our data suggest that the immune modulatory properties of CSCs and LSCs here described in vitro for the first time may have a role in vivo in favoring their regenerative potential. Secondly, both CSCs and LSCs become structurally and functionally coupled with the cells of the recipient organ, creating new niches in which the SCs can divide asymmetrically [73,75,76], thus ensuring the preservation of the SC pool and the formation of parenchymal and vascular cells [50,53,77]. It is likely that the potential clinical implementation of these SC populations is significantly strengthened by their immunomodulatory function.…”

Heart regeneration after myocardial infarction using synthetic biomaterials

“…The discrepancies in the results of different clinical trials using the same cell source have led researches to investigate the key aspects that determine the success of cell therapy. A careful analysis of the available data shows that negative results may be fundamentally due to the poor permanence of the injected cells inside the tissue [21,22], since SCs therapeutic efficacy depend on their ability to survive in the hostile milieu of the damaged heart and to engraft within the myocardium [23]. Another critical point is the complexity of obtaining a reliable source of functional CMCs.…”

Use of Stem Cells in Heart Failure Treatment: Where We Stand and Where We Are Going

“…Moreover, the effect of the addition of BMCs by intracoronary or intramyocardial injection on these results has been tested in a few studies. [31][32][33] zhang et al 34 performed a meta-analysis of 11 clinical trials that evaluated the efficacy of autologous BMC transfer in 490 total patients with chronic ischemic heart disease. Compared with controls, BMC-treated patients significantly improved lveF by 4.63% and showed a significant reduction in lvedv and lvesv.…”