Stem cells for heart cell therapies

Abstract

Myocardial infarction-induced heart failure is a prevailing cause of death in the United States and most developed countries. The cardiac tissue has extremely limited regenerative potential, and heart transplantation for reconstituting the function of damaged heart is severely hindered mainly due to the scarcity of donor organs. To that end, stem cells with their extensive proliferative capacity and their ability to differentiate toward functional cardiomyocytes may serve as a renewable cellular source for repairing the damaged myocardium. Here, we review recent studies regarding the cardiogenic potential of adult progenitor cells and embryonic stem cells. Although large strides have been made toward the engineering of cardiac tissues using stem cells, important issues remain to be addressed to enable the translation of such technologies to the clinical setting.

FIG. 1.

Potential sources of stem/progenitor cells for cardiac repair. ESCs derived from the inner cell mass of a blastocyst can be manipulated ex vivo to differentiate toward heart cells. APCs residing in various tissues such as the BM and skeletal muscle may also serve as a source of heart cells. Progenitor cells have also been identified in the heart and may contribute to its regeneration. Color images available online at www.liebertonline.com/ten.

FIG. 2.

Representative stages of cardiac cell differentiation. Some of the known inductive (→) and inhibitory (⊥) signals involved at different stages of embryonic heart development are shown. Major markers at each stage are also depicted.

FIG. 3.

(A) Schematic of cardiogenic differentiation of ESCs. Cells are cultured in low adhesion surfaces to form EBs. Then, EBs are transferred to adhesive substrata (e.g., gelatin-coated tissue culture dishes) and spread forming outgrowths. Beating foci are observed as early as 2 weeks (for hESCs) or 2 days (for mESCs) after EB plating. H9 hESCs are shown at different stages of differentiation. (B) The fraction of beating EBs (mean ± SD; n = 15–25 fields of view) in differentiating mESC cultures increases and reaches almost 100% within 10 days after EB plating. Differentiation is performed in FBS-containing medium and 1 nM retinoic acid as described before. (C) Differentiated ESCs express cardiomyocyte-specific proteins such as NKX2.5 (magnification: 400×) and cTnI (bar: 20 μm). Color images available online at www.liebertonline.com/ten.