Regeneration Next: Toward Heart Stem Cell Therapeutics Emil M. Hansson, Mark E. Lindsay, Kenneth R. Chien  Cell Stem Cell  Volume 5, Issue 4, Pages 364-377 (October 2009) DOI: 10.1016/j.stem.2009.09.004 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 The Heart Is a Mosaic of Cells from Different Progenitor Populations The heart is composed of cells derived from at least four different populations of progenitor cells—the first heart field progenitor cells (blue), the second heart field progenitor cells (red), the epicardial progenitor cells (yellow), and the cardiac neural crest progenitor cells (green). Progeny from these progenitor pools reside in distinct but partly overlapping areas in the mature heart. Cell Stem Cell 2009 5, 364-377DOI: (10.1016/j.stem.2009.09.004) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 2 Experimental Approaches to Cardiac Cell Therapy Clinical trials have been conducted with satellite cells and preparations of bone marrow cells, that have been delivered to the failing heart. Such treatments have failed to increase the number of cardiomyocytes in the heart. Conceptually this would be possible to achieve by purifying cells of the cardiac lineage from differentiating ESCs or iPSCs, or by direct reprogramming of somatic cells to the relevant cell type, and thereafter transplanting such cells to the heart of the patient. Cell Stem Cell 2009 5, 364-377DOI: (10.1016/j.stem.2009.09.004) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 3 Schematic Illustration of Cardiac Outflow Tract Development and Its Relation to Congenital Heart Disease The outflow tract is derived largely from SHF progenitor cells with more distal contributions from cardiac neural crest. Disturbances in the proliferation and differentiation of ISL1-expressing progenitor cells disrupt developmental morphogenic functionality and cause malformations of the outflow tract seen in patients with congenital heart disease (blue arrows). Several genes, when mutated, are known to cause these prototypical outflow tract malformations: double outlet right ventricle (NKX2.5, THRAP2, and CHD7), transposition of the great arteries (NKX2.5, GDF1 and CHD7), persistent truncus arteriosus (NKX2.5, TBX1, NOTCH1 and NOTCH2, JAGGED1, GDF1, THRAP2, and CHD7), and aortic stenosis (NOTCH1). A-P, aorto-pulmonary. Cell Stem Cell 2009 5, 364-377DOI: (10.1016/j.stem.2009.09.004) Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 4 Ex Vivo Construction of ESC-Derived RV-PA Conduit Implantation of a conduit to substitute for an atretic great artery is needed for several different congenital lesions including pulmonary atresia. Combining advances in ESC or iPSC technology to derive SHF-specific vascular smooth muscle cells with described tissue-engineering solutions could provide proper lineage-derived conduits with growth capacity. Cell Stem Cell 2009 5, 364-377DOI: (10.1016/j.stem.2009.09.004) Copyright © 2009 Elsevier Inc. Terms and Conditions