Embryonic and embryonic-like stem cells in heart muscle engineering.
Cardiac muscle engineering is evolving rapidly and may ultimately be exploited to (1) model cardiac development, physiology, and pathology; (2) identify and validate drug targets; (3) assess drug safety and efficacy; and (4) provide therapeutic substitute myocardium. The ultimate success in any of these envisioned applications depends on the utility of human cells and their assembly into myocardial equivalents with structural and functional properties of mature heart muscle. Embryonic stem cells appear as a promising cell source in this respect, because they can be cultured reliably and differentiated robustly into cardiomyocytes. Despite their unambiguous cardiogenicity, data on advanced maturation and seamless myocardial integration of embryonic stem cell-derived cardiomyocytes in vivo are sparse. Additional concerns relate to the limited control over cardiomyogenic specification and cardiomyocyte maturation in vitro as well as the risk of teratocarcinoma formation and immune rejection of stem cell implants in vivo. Through the invent of embryonic-like stem cells - such as parthenogenetic stem cells, male germline stem cells, and induced pluripotent stem cells - some but certainly not all of these issues may be addressed, albeit at the expense of additional concerns. This review will discuss the applicability of embryonic and embryonic-like stem cells in myocardial tissue engineering and address issues that require particular attention before the potential of stem cell-based heart muscle engineering may be fully exploited. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".
Department of Pharmacology, University Medical Center Göttingen, Georg-August-University Göttingen, Goettingen, Germany. w.zimmermann@med.uni-goettingen.de
Wolfram-Hubertus
WH
Zimmermann
D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods; D023822:Tissue Engineering