HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Shinji Tomita Soichiro Kitamura Takeshi Nakatani Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fukuhara, S. Articles by Nakatani, T. Search for Related Content PubMed PubMed Citation Articles by Fukuhara, S. Articles by Nakatani, T. Related Collections Molecular biology

J Thorac Cardiovasc Surg 2003;125:1470-1480
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Direct cell-cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro

From the Department of Pathology, National Cardiovascular Center, Osaka^a; the Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka^b; the Department of General Medicine, Saga Medical School, Saga^c; the Department of Bioscience, National Cardiovascular Center, Research Institute, Osaka^d; and the Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan.^e

Supported in part by Health Sciences Research Grants (Research for Cardiovascular Diseases [13C-1] and Research on the Human Genome, Tissue Engineering Food Biotechnology [12-007]) from the Ministry of Health, Labor, and Welfare, and by Grant-in-Aid for Scientific Research (A) and for Exploratory Research from the Japan Society for the Promotion of Science.

Received for publication June 5, 2002. Revisions requested Aug 5, 2002; revisions received Sept 1, 2002. Accepted for publication Oct 10, 2002. Address for reprints: Shinji Tomita, MD, Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan (E-mail: shinjitomita{at}hotmail.com).

Objectives: Cardiac environmental factors are thought to be powerful inducers in cardiomyogenic differentiation. In this study we simulated the cardiac environment using coculture and evaluated the cardiomyogenic differentiation in bone marrow stromal cells.
Methods: In group 1 only bone marrow stromal cells derived from transgenic mice expressing green fluorescent protein (GFP-BMCs) were cultured (n = 5). In group 2 cardiomyocytes from neonatal rats were grown on inserts, which we applied to culture dishes seeded with GFP-BMCs (n = 5). In group 3 GFP-BMCs were cocultured with cardiomyocytes on the same dishes (n = 5). We cultured these cells for 7 days and evaluated the synchronous contraction and the cardiomyogenic differentiation of GFP-BMCs by means of immunostaining.
Results: In groups 1 and 2 GFP-BMCs protein did not show any myogenic phenotypes for 7 days. In contrast, in group 3 some GFP-BMCs were incorporated in parallel with cardiomyocytes and revealed myotube-like formation on day 1. On day 2, some GFP-BMCs started to contract synchronously with cardiomyocytes. Myosin heavy chain-positive GFP-BMCs were recognized in 2.49% ± 0.87% of the total GFP-BMCs on day 5 (P < .0001). Cardiac-specific troponin I-positive GFP-BMCs were in 1.86% ± 0.53% of the total cells on day 5 (P < .0001). Atrial natriuretic peptide was also seen in GFP-BMCs, and connexin 43 was detected between GFP-BMCs and cardiomyocytes.
Conclusions: Direct cell-cell interaction with cardiomyocytes was important for bone marrow stromal cells to differentiate into cardiomyocytes. This coculture was useful for simulating the cardiac environment in vitro for the research of cell transplantation in the heart.

This article has been cited by other articles:

				R. L Kao, W. Browder, and C. Li Cellular Cardiomyoplasty: What Have We Learned? Asian Cardiovasc Thorac Ann, January 1, 2009; 17(1): 89 - 101. [Abstract] [Full Text] [PDF]

				R. A. Rose, H. Jiang, X. Wang, S. Helke, J. N. Tsoporis, N. Gong, S. C.J. Keating, T. G. Parker, P. H. Backx, and A. Keating Bone Marrow-Derived Mesenchymal Stromal Cells Express Cardiac-Specific Markers, Retain the Stromal Phenotype, and Do Not Become Functional Cardiomyocytes In Vitro Stem Cells, November 1, 2008; 26(11): 2884 - 2892. [Abstract] [Full Text] [PDF]

				N. Derval, L. Barandon, P. Dufourcq, L. Leroux, J.-M. D. Lamaziere, D. Daret, T. Couffinhal, and C. Duplaa Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model. Eur. J. Cardiothorac. Surg., August 1, 2008; 34(2): 248 - 254. [Abstract] [Full Text] [PDF]

				A. Orlandi, F. Pagani, D. Avitabile, G. Bonanno, G. Scambia, E. Vigna, F. Grassi, F. Eusebi, S. Fucile, M. Pesce, et al. Functional properties of cells obtained from human cord blood CD34+ stem cells and mouse cardiac myocytes in coculture Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1541 - H1549. [Abstract] [Full Text] [PDF]

				R. Atoui, J.-F. Asenjo, M. Duong, G. Chen, R. C.-J. Chiu, and D. Shum-Tim Marrow Stromal Cells as Universal Donor Cells for Myocardial Regenerative Therapy: Their Unique Immune Tolerance Ann. Thorac. Surg., February 1, 2008; 85(2): 571 - 579. [Abstract] [Full Text] [PDF]

				V. L.T. Ballard and J. M. Edelberg Stem Cells and the Regeneration of the Aging Cardiovascular System Circ. Res., April 27, 2007; 100(8): 1116 - 1127. [Abstract] [Full Text] [PDF]

				J. J. Minguell and A. Erices Mesenchymal Stem Cells and the Treatment of Cardiac Disease Experimental Biology and Medicine, January 1, 2006; 231(1): 39 - 49. [Abstract] [Full Text] [PDF]

				D. J. MacDonald, J. Luo, T. Saito, M. Duong, P.-L. Bernier, R. C.J. Chiu, and D. Shum-Tim Persistence of marrow stromal cells implanted into acutely infarcted myocardium: Observations in a xenotransplant model J. Thorac. Cardiovasc. Surg., October 1, 2005; 130(4): 1114 - 1121. [Abstract] [Full Text] [PDF]

				H. K. Haider and M. Ashraf Bone marrow stem cell transplantation for cardiac repair Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2557 - H2567. [Abstract] [Full Text] [PDF]

				A. J. Rastan, T. Walther, M. Kostelka, J. Garbade, A. Schubert, A. Stein, S. Dhein, and F. W. Mohr Morphological, electrophysiological and coupling characteristics of bone marrow-derived mononuclear cells--an in vitro-model Eur. J. Cardiothorac. Surg., January 1, 2005; 27(1): 104 - 110. [Abstract] [Full Text] [PDF]

				N. Nagaya, T. Fujii, T. Iwase, H. Ohgushi, T. Itoh, M. Uematsu, M. Yamagishi, H. Mori, K. Kangawa, and S. Kitamura Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2670 - H2676. [Abstract] [Full Text] [PDF]

				M. Xaymardan, L. Tang, L. Zagreda, B. Pallante, J. Zheng, J. L. Chazen, A. Chin, I. Duignan, P. Nahirney, S. Rafii, et al. Platelet-Derived Growth Factor-AB Promotes the Generation of Adult Bone Marrow-Derived Cardiac Myocytes Circ. Res., March 19, 2004; 94(5): e39 - e45. [Abstract] [Full Text] [PDF]

				J. C. Chachques, C. Acar, J. Herreros, J. C. Trainini, F. Prosper, N. D'Attellis, J.-N. Fabiani, and A. F. Carpentier Cellular cardiomyoplasty: clinical application Ann. Thorac. Surg., March 1, 2004; 77(3): 1121 - 1130. [Abstract] [Full Text] [PDF]