| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
E-mail contact: murry@u.washington.edu
Embryonic stem (ES) cells are promising for cardiac repair, but directing their differentiation toward cardiomyocytes remains challenging. We investigated whether the heart guides ES cells toward cardiomyocytes in vivo and whether allogeneic ES cells were immunologically tolerated. Undifferentiated mouse ES cells consistently formed cardiac teratomas in nude or immunocompetent syngeneic mice. Cardiac teratomas contained no more cardiomyocytes than hind-limb teratomas, suggesting lack of guided differentiation. ES cells also formed teratomas in infarcted hearts, indicating injury-related signals did not direct cardiac differentiation. Allogeneic ES cells also caused cardiac teratomas, but these were immunologically rejected after several weeks, in association with increased inflammation and up-regulation of class I and II histocompatibility antigens. Fusion between ES cells and cardiomyocytes occurred in vivo, but was rare. Infarct autofluorescence was identified as an artifact that might be mistaken for enhanced GFP expression and true regeneration. Hence, undifferentiated ES cells were not guided toward a cardiomyocyte fate in either normal or infarcted hearts, and there was no evidence for allogeneic immune tolerance of ES cell derivatives. Successful cardiac repair strategies involving ES cells will need to control cardiac differentiation, avoid introducing undifferentiated cells, and will likely require immune modulation to avoid rejection.--Nussbaum, J., Minami, E., Laflamme, M. A., Virag, J. A. I., Ware C. B., Masino, A., Muskheli, V., Pabon, L., Reinecke, H., Murry, C. E. Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response.
Related Articles
This article has been cited by other articles:
|
|
 |
|
  J. Lee and C. M. Terracciano Cell therapy for cardiac repair Br. Med. Bull., March 2, 2010; (2010) ldq005v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Herrmann, A. M. Abarbanell, B. R. Weil, Y. Wang, M. Wang, J. Tan, and D. R. Meldrum Cell-based therapy for ischemic heart disease: a clinical update. Ann. Thorac. Surg., November 1, 2009; 88(5): 1714 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Van Orman, D. Weihrauch, D. C. Warltier, and J. Lough Myocardial interstitial fluid inhibits proliferation and cardiomyocyte differentiation in pluripotent embryonic stem cells Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1369 - H1376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Dixon, R. C. Gorman, R. E. Stroud, S. Bouges, H. Hirotsugu, J. H. Gorman III, T. P. Martens, S. Itescu, M. D. Schuster, T. Plappert, et al. Mesenchymal Cell Transplantation and Myocardial Remodeling After Myocardial Infarction Circulation, September 15, 2009; 120(11_suppl_1): S220 - S229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Smits, L. W. van Laake, K. den Ouden, C. Schreurs, K. Szuhai, C. J. van Echteld, C. L. Mummery, P. A. Doevendans, and M.-J. Goumans Human cardiomyocyte progenitor cell transplantation preserves long-term function of the infarcted mouse myocardium Cardiovasc Res, August 1, 2009; 83(3): 527 - 535. [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]
|
|
|
|
 |
|
 R. L Kao, W. Browder, and C. Li Cellular Cardiomyoplasty: What Have We Learned? Asian Cardiovasc Thorac Ann, February 1, 2009; 17(1): 89 - 101. [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]
|
|
|
|
 |
|
 H. Reinecke, E. Minami, W.-Z. Zhu, and M. A. Laflamme Cardiogenic Differentiation and Transdifferentiation of Progenitor Cells Circ. Res., November 7, 2008; 103(10): 1058 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Hendry II, K. E.A. van der Bogt, A. Y. Sheikh, T. Arai, S. J. Dylla, M. Drukker, M. V. McConnell, I. Kutschka, G. Hoyt, F. Cao, et al. Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells. J. Thorac. Cardiovasc. Surg., October 1, 2008; 136(4): 1028 - 1037.e1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Tulloch, L. Pabon, and C. E. Murry Get With the (Re)Program: Cardiovascular Potential of Skin-Derived Induced Pluripotent Stem Cells Circulation, July 29, 2008; 118(5): 472 - 475. [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Cho, S.-H. Moon, S.-H. Lee, S.-W. Kang, J. Kim, J. M. Lim, H.-S. Kim, B.-S. Kim, and H. M. Chung Improvement of Postnatal Neovascularization by Human Embryonic Stem Cell-Derived Endothelial-Like Cell Transplantation in a Mouse Model of Hindlimb Ischemia Circulation, November 20, 2007; 116(21): 2409 - 2419. [Abstract] [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]
|
|
|
|
 |
|
 A. Behfar and A. Terzic Cardioprotective repair through stem cell-based cardiopoiesis J Appl Physiol, October 1, 2007; 103(4): 1438 - 1440. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
