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) All Versions of this Article: 2006-0168v1 25/3/612    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakamura, Y. Articles by Zhang, J. Search for Related Content PubMed PubMed Citation Articles by Nakamura, Y. Articles by Zhang, J.

TISSUE-SPECIFIC STEM CELLS

Xenotransplantation of Long-Term-Cultured Swine Bone Marrow-Derived Mesenchymal Stem Cells

^aCardiovascular Division, Departments of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA;
^bDepartment of Internal Medicine and Cardiology, Osaka City University Medical School, Osaka, Japan

Key Words. Cell culture • Mesenchymal stem cell lines • Therapeutic efficacy • Myocardial infarction • Heart

Correspondence: Jianyi Zhang, M.D., Ph.D., University of Minnesota Academic Health Center, Mayo Mail Code 508, 420 Delaware Street SE, Minneapolis, Minnesota 55455, USA. Telephone: 612-624-8970; Fax: 612-626-4411; e-mail: zhang047{at}umn.edu

Received March 22, 2006; accepted for publication November 4, 2006.
First published online in STEM CELLS EXPRESS   November 9, 2006.



Swine-derived MSCs were efficiently isolated and extensively expanded using a low fetal serum content growth medium to which selected growth factors were added. After 96 cell population doublings (PDs), MSCs were devoid of cytogenetic abnormalities. In vitro chondrogenic and osteogenic differentiation capacity was preserved after 80 PDs. To test therapeutic efficacy, 1 x 10⁶ 80-PD MSCs were injected directly into the peri-infarct zone of hearts of immunodeficient (non-obese diabetic/severe combined immunodeficient) mice at the time of acute myocardial infarction. Engrafted MSCs survived in the infarcted hearts for at least 4 weeks. Echocardiography at 2 and 4 weeks postinfarction revealed a significant preservation of the left ventricular ejection fractions of infarct hearts receiving MSCs compared with infarct hearts receiving saline. Peri-infarct zone capillarity was better preserved in MSC-treated hearts than other infarct groups of hearts, but infarct size was comparable in all groups. Only rare engrafted MSCs expressed cardiac-specific or endothelial cell-specific markers. Hence, 80-PD MSCs retained the capacity to promote functional improvement in the infarcted heart despite minimal differentiation of MSCs into cardiomyocytes or endothelial cells. These data suggest that the beneficial effects of MSC transplantation most likely result from the trophic effects of MSC-released substances on native cardiac and vascular cells. The capacity to massively expand MSC lines without loss of therapeutic efficacy may prove to be useful in the clinical setting where "off the shelf" MSCs may be required for interventions in patients with acute coronary syndromes.

This article has been cited by other articles:

				M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy Circ. Res., November 21, 2008; 103(11): 1204 - 1219. [Abstract] [Full Text] [PDF]

				S.-A Chang, E. J. Lee, H.-J. Kang, S.-Y. Zhang, J.-H. Kim, L. Li, S.-W. Youn, C.-S. Lee, K.-H. Kim, J.-Y. Won, et al. Impact of Myocardial Infarct Proteins and Oscillating Pressure on the Differentiation of Mesenchymal Stem Cells: Effect of Acute Myocardial Infarction on Stem Cell Differentiation Stem Cells, July 1, 2008; 26(7): 1901 - 1912. [Abstract] [Full Text] [PDF]

				R. W. Grauss, J. van Tuyn, P. Steendijk, E. M. Winter, D. A. Pijnappels, B. Hogers, A. C. Gittenberger-De Groot, R. van der Geest, A. van der Laarse, A. A.F. de Vries, et al. Forced Myocardin Expression Enhances the Therapeutic Effect of Human Mesenchymal Stem Cells After Transplantation in Ischemic Mouse Hearts Stem Cells, April 1, 2008; 26(4): 1083 - 1093. [Abstract] [Full Text] [PDF]

				S. N. Ebert, D. G. Taylor, H.-L. Nguyen, D. P. Kodack, R. J. Beyers, Y. Xu, Z. Yang, and B. A. French Noninvasive Tracking of Cardiac Embryonic Stem Cells In Vivo Using Magnetic Resonance Imaging Techniques Stem Cells, November 1, 2007; 25(11): 2936 - 2944. [Abstract] [Full Text] [PDF]

				R. W. Grauss, E. M. Winter, J. van Tuyn, D. A. Pijnappels, R. V. Steijn, B. Hogers, R. J. van der Geest, A. A. F. de Vries, P. Steendijk, A. van der Laarse, et al. Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2438 - H2447. [Abstract] [Full Text] [PDF]

				A. C. Boquest, A. Noer, A. L. Sorensen, K. Vekterud, and P. Collas CpG Methylation Profiles of Endothelial Cell-Specific Gene Promoter Regions in Adipose Tissue Stem Cells Suggest Limited Differentiation Potential Toward the Endothelial Cell Lineage Stem Cells, April 1, 2007; 25(4): 852 - 861. [Abstract] [Full Text] [PDF]