How to Stimulate Myocardial Regeneration in Adult Mammalian Heart: Existing Views and New Approaches

Figure 1

Novel strategies for CSC-based myocardial repair. Schematic overviews of current strategies used to make use of CSCs for myocardial repair are shown in a compilation of previously published figures [12, 13] with some modifications provided by us. Strategy 1 is based on activation of endogenous CSCs by various means, e.g., (a) growth factors, (b) noncardiac stem cells, or (c) gene therapy. Strategy 1(a): upon activation, resident endogenous CSCs can proliferate and mature into newly formed cardiac myocytes (green cardiac myocytes). Strategy 1(b) is based on activation of endogenous CSC colonies and CSC CICSs with formation of TACs. Strategy 2(c) is based on the delivery of autologous CSCs that have been isolated from small myocardial biopsies and scaled up outside the patient to sufficient numbers. Exogenous CSCs are also shown to be capable of activating the local endogenous CSC compartment. Strategy 2(d) is based on the delivery of autologous CICSs that have been isolated from small myocardial biopsies and scaled up outside the patient to sufficient numbers. In addition, exogenously delivered CSCs and CICSs are hypothesized to mature and differentiate into functional cardiac myocytes (yellow cardiac myocytes) that are electromechanically coupled with the preexisting cardiac myocytes (orange cardiac myocytes) [12]. Abbreviations: CSC: cardiac stem/progenitor cell; CICS: cell-in-cell structure; TACs: transitory amplifying cells.