| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |





From the Department of Pathology,* University of Washington, Seattle, Washington; and Geron Corporation,
Menlo Park, California
Human embryonic stem cells (hESCs) offer the opportunity to replenish cells lost in the postinfarct heart. We explored whether human myocardium could be generated in rat hearts by injecting differentiated cardiac-enriched hESC progeny into the left ventricular wall of athymic rats. Although initial grafts were predominantly epithelial, noncardiac elements were lost over time, and grafts consisted predominantly of cardiomyocytes by 4 weeks. No teratomatous elements were observed. Engrafted cardiomyocytes were glycogen-rich and expressed expected cardiac markers including ß-myosin heavy chain, myosin light chain 2v, and atrial natriuretic factor. Heat-shock treatment improved graft size approximately threefold. The cardiac implants exhibited substantial angiogenesis, both recipient and graft derived. Importantly, there was greater proliferation in human cardiomyocytes than previously seen in rodent-derived cardiomyocytes: 14.4% of graft cardiomyocytes expressed the proliferation marker Ki-67, and 2.7% incorporated the thymidine analog BrdU 4 weeks after transplantation. This proliferation was associated with a sevenfold increase in graft size over the 4-week interval. Thus, hESCs can form human myocardium in the rat heart, permitting studies of human myocardial development and physiology and supporting the feasibility of their use in myocardial repair.
This article has been cited by other articles:
![]() |
M. B. Nourse, D. E. Halpin, M. Scatena, D. J. Mortisen, N. L. Tulloch, K. D. Hauch, B. Torok-Storb, B. D. Ratner, L. Pabon, and C. E. Murry VEGF Induces Differentiation of Functional Endothelium From Human Embryonic Stem Cells: Implications for Tissue Engineering Arterioscler Thromb Vasc Biol, January 1, 2010; 30(1): 80 - 89. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. D. Boudoulas and A. K. Hatzopoulos Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease Dis. Model. Mech., July 1, 2009; 2(7-8): 344 - 358. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Habeler, S. Pouillot, A. Plancheron, M. Puceat, M. Peschanski, and C. Monville An in vitro beating heart model for long-term assessment of experimental therapeutics Cardiovasc Res, February 1, 2009; 81(2): 253 - 259. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Raya, I. Rodriguez-Piza, B. Aran, A. Consiglio, P.N. Barri, A. Veiga, and J.C. Izpisua Belmonte Generation of Cardiomyocytes from New Human Embryonic Stem Cell Lines Derived from Poor-quality Blastocysts Cold Spring Harb Symp Quant Biol, November 26, 2008; (2008) sqb.2008.73.038v2. [Abstract] [PDF] |
||||
![]() |
N. Takayama, H. Nishikii, J. Usui, H. Tsukui, A. Sawaguchi, T. Hiroyama, K. Eto, and H. Nakauchi Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors Blood, June 1, 2008; 111(11): 5298 - 5306. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Smart and P. R. Riley The Stem Cell Movement Circ. Res., May 23, 2008; 102(10): 1155 - 1168. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. S. Jovin and F. J. Giordano Differentiation by association: is a cell's fate determined by the company it keeps? Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1503 - H1504. [Full Text] [PDF] |
||||
![]() |
O. Caspi, I. Huber, I. Kehat, M. Habib, G. Arbel, A. Gepstein, L. Yankelson, D. Aronson, R. Beyar, and L. Gepstein Transplantation of Human Embryonic Stem Cell-Derived Cardiomyocytes Improves Myocardial Performance in Infarcted Rat Hearts J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1884 - 1893. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Janssens Human embryonic stem cells for cardiac repair: the focus is on refined selection and cardiopoietic programming Heart, October 1, 2007; 93(10): 1173 - 1174. [Full Text] [PDF] |
||||
![]() |
J. Leor, S. Gerecht, S. Cohen, L. Miller, R. Holbova, A. Ziskind, M. Shachar, M. S Feinberg, E. Guetta, and J. Itskovitz-Eldor Human embryonic stem cell transplantation to repair the infarcted myocardium Heart, October 1, 2007; 93(10): 1278 - 1284. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Nussbaum, E. Minami, M. A. Laflamme, J. A. I. Virag, C. B. Ware, A. Masino, V. Muskheli, L. Pabon, H. Reinecke, and C. E. Murry Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response FASEB J, May 1, 2007; 21(7): 1345 - 1357. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Behfar, C. Perez-Terzic, R. S. Faustino, D. K. Arrell, D. M. Hodgson, S. Yamada, M. Puceat, N. Niederlander, A. E Alekseev, L. V. Zingman, et al. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair J. Exp. Med., February 19, 2007; 204(2): 405 - 420. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Norstrom, K. Akesson, T. Hardarson, L. Hamberger, P. Bjorquist, and P. Sartipy Molecular and Pharmacological Properties of Human Embryonic Stem Cell-Derived Cardiomyocytes Exp Biol Med, December 1, 2006; 231(11): 1753 - 1762. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. W. van Laake, R. Hassink, P. A. Doevendans, and C. Mummery Heart repair and stem cells J. Physiol., December 1, 2006; 577(2): 467 - 478. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Kolossov, T. Bostani, W. Roell, M. Breitbach, F. Pillekamp, J. M. Nygren, P. Sasse, O. Rubenchik, J. W. U. Fries, D. Wenzel, et al. Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium J. Exp. Med., October 2, 2006; 203(10): 2315 - 2327. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Caspi and L. Gepstein Stem cells for myocardial repair Eur. Heart J. Suppl., September 1, 2006; 8(suppl_E): E43 - E54. [Abstract] [Full Text] [PDF] |
||||
![]() |
E.C. Spikings, J. Alderson, and J.C.St. John Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer Hum. Reprod. Update, July 1, 2006; 12(4): 401 - 415. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. E. Murry, H. Reinecke, and L. M. Pabon Regeneration Gaps: Observations on Stem Cells and Cardiac Repair J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1777 - 1785. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. A. Kloner Attempts to Recruit Stem Cells for Repair of Acute Myocardial Infarction: A Dose of Reality JAMA, March 1, 2006; 295(9): 1058 - 1060. [Full Text] [PDF] |
||||
![]() |
C. E. Murry, L. J. Field, and P. Menasche Cell-Based Cardiac Repair: Reflections at the 10-Year Point Circulation, November 15, 2005; 112(20): 3174 - 3183. [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |