Cellular cardiomyoplasty—cardiomyocytes, skeletal myoblasts, or stem cells for regenerating myocardium and treatment of heart failure?
Authors: T Reffelmann
Journal: Cardiovascular Research (2003)

. Introductionto prevent extensive scar formation and the relentless disease progression of heart failure after myocardial infarc-In newts, excision of up to 50% of the ventricular tion or loss of contractile function with pressure or volume myocardium results in spontaneous regeneration and re-overload [18,19].Despite progress in pharmacological building of the heart, a process that involves de-differentia-treatment of the syndrome of heart failure [20], mortality tion of the remaining cardiomyocytes, de-novo synthesis of and curtailment of quality of life in advanced stages of DNA followed by proliferation and mitotic cell division of congestive heart failure are significant [21], and the both cardiomyocytes and connective tissue, and subsequent question remains, whether additional approaches can be replacing of the lost tissue [1][2][3].In contrast, the mam-developed for repairing human myocardial tissue.malian heart loses its capability of a quantitatively suffi-Taking the newt as a model of regenerating irreversibly cient proliferative response to various injuries soon after damaged myocardium, the features of de-differentiation, birth [4][5][6].Interestingly, recent studies reported a certain proliferation, and re-differentiation, might be the basis for degree of cardiomyocyte regeneration in various developing strategies for repairing and rebuilding the pathologic conditions, such as heart failure [7], orthotopic failing human heart: Presumably, the most desirable future heart transplantation [8,9], or myocardial infarction goal would be the identification of the cellular and [10,11], and even surmised the existence of resident molecular mechanisms that prevent the adult mammalian cardiac stem cells [12], or extracardiac cardiomyocyte cardiomyocyte from re-entering the cell cycle after loss of progenitor cells [13] in the mammalian heart.However, contractile tissue leading to therapeutic strategies that force these findings are still controversial [14].In some of these surviving cardiomyocytes to de-differentiate, proliferate, studies, the presence of the Y-chromosome in hearts from and re-differentiate after myocardial damage [5,22].Howfemale donors after gender-incompatible heart transplanta-ever, another innovative approach, probably within nearer tion was used as evidence for population of the hearts by reach, is the exogenous delivery of less differentiated cells extracardiac progenitors.However, recent in vitro studies to the damaged heart, that retain to a certain degree their reported the occurrence of spontaneous cell fusions of capability of proliferation, and subsequently may colonise putative stem cells, such as bone-marrow [15] or neural the scar and differentiate into cells with contractile propstem cells [16], with embryonic stem cells when cultured erties.together, which challenges the concept of transdifferention This review will try to characterise the results of recent and requires additional investigations in this field.attempts to rebuild injured myocardial tissue by transplant-Nevertheless, the mechanisms of re-activated or pre-ing cells of various origin and stage of differentiation, such served cardiomyocyte proliferation and regeneration in as fetal and neonatal cardiomyocytes, skeletal myoblasts, humans (for review see [17]) are obviously not sufficient and embryonic and mesenchymal stem cells.Advantages, disadvantages, and major obstacles of using cells of various levels of differentiation are discussed.