|
|
||||||||
Ann Thorac Surg 2002;73:1919-1926
© 2002 The Society of Thoracic Surgeons
a The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
b Osiris Therapeutics, Inc, Baltimore, Maryland, USA
* Address reprint requests to Dr Martin, Osiris Therapeutics, Inc, 2001 Aliceanna St, Baltimore, MD 21231 USA
e-mail: bmartin{at}osiristx.com
Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 2931, 2001.
Background. A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model.
Methods. MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-Ilabeled MSCs (6 x 107) were implanted into the infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation.
Results. Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% ± 2.2% versus -3.37% ± 2.7% in control). In addition, the extent of wall thinning after myocardial infarction was markedly reduced in treated animals.
Conclusions. Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with myocardial infarction.
This article has been cited by other articles:
![]() |
P. J. Psaltis, A. C.W. Zannettino, S. G. Worthley, and S. Gronthos Concise Review: Mesenchymal Stromal Cells: Potential for Cardiovascular Repair Stem Cells, September 1, 2008; 26(9): 2201 - 2210. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. B. Copland, E. M. Jolicoeur, M.-A. Gillis, J. Cuerquis, N. Eliopoulos, B. Annabi, A. Calderone, J.-F. Tanguay, A. Ducharme, and J. Galipeau Coupling erythropoietin secretion to mesenchymal stromal cells enhances their regenerative properties Cardiovasc Res, August 1, 2008; 79(3): 405 - 415. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Hida, N. Nishiyama, S. Miyoshi, S. Kira, K. Segawa, T. Uyama, T. Mori, K. Miyado, Y. Ikegami, C. Cui, et al. Novel Cardiac Precursor-Like Cells from Human Menstrual Blood-Derived Mesenchymal Cells Stem Cells, July 1, 2008; 26(7): 1695 - 1704. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Eliopoulos, M. Francois, M.-N. Boivin, D. Martineau, and J. Galipeau Neo-Organoid of Marrow Mesenchymal Stromal Cells Secreting Interleukin-12 for Breast Cancer Therapy Cancer Res., June 15, 2008; 68(12): 4810 - 4818. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. A. Mylotte, A. M. Duffy, M. Murphy, T. O'Brien, A. Samali, F. Barry, and E. Szegezdi Metabolic Flexibility Permits Mesenchymal Stem Cell Survival in an Ischemic Environment Stem Cells, May 1, 2008; 26(5): 1325 - 1336. [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] |
||||
![]() |
J.-Y. Hahn, H.-J. Cho, H.-J. Kang, T.-S. Kim, M.-H. Kim, J.-H. Chung, J.-W. Bae, B.-H. Oh, Y.-B. Park, and H.-S. Kim Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction. J. Am. Coll. Cardiol., March 4, 2008; 51(9): 933 - 943. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Shujia, H. K. Haider, N. M. Idris, G. Lu, and M. Ashraf Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair Cardiovasc Res, February 1, 2008; 77(3): 525 - 533. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. Hashemi, S. Ghods, F. D. Kolodgie, K. Parcham-Azad, M. Keane, D. Hamamdzic, R. Young, M. K. Rippy, R. Virmani, H. Litt, et al. A placebo controlled, dose-ranging, safety study of allogenic mesenchymal stem cells injected by endomyocardial delivery after an acute myocardial infarction Eur. Heart J., January 2, 2008; 29(2): 251 - 259. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. Gallegos and R. M. Bolman III Stem Cell Induced Regeneration of Myocardium Card. Surg. Adult, January 1, 2008; 3(2008): 1657 - 1668. [Full Text] |
||||
![]() |
Z. H. Zheng, X. Y. Li, J. Ding, J. F. Jia, and P. Zhu Allogeneic mesenchymal stem cell and mesenchymal stem cell-differentiated chondrocyte suppress the responses of type II collagen-reactive T cells in rheumatoid arthritis. Rheumatology, January 1, 2008; 47(1): 22 - 30. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Chen, A. R. Baydoun, R. Xu, L. Deng, X. Liu, W. Zhu, L. Shi, X. Cong, S. Hu, and X. Chen Lysophosphatidic Acid Protects Mesenchymal Stem Cells Against Hypoxia and Serum Deprivation-Induced Apoptosis Stem Cells, January 1, 2008; 26(1): 135 - 145. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Pasha, Y. Wang, R. Sheikh, D. Zhang, T. Zhao, and M. Ashraf Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium Cardiovasc Res, January 1, 2008; 77(1): 134 - 142. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Zhang, N. Mal, M. Kiedrowski, M. Chacko, A. T. Askari, Z. B. Popovic, O. N. Koc, and M. S. Penn SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction FASEB J, October 1, 2007; 21(12): 3197 - 3207. [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] |
||||
![]() |
J. Makela, K. Ylitalo, S. Lehtonen, S. Dahlbacka, E. Niemela, K. Kiviluoma, J. Rimpilainen, H. Alaoja, T. Paavonen, P. Lehenkari, et al. Bone marrow derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site J. Thorac. Cardiovasc. Surg., September 1, 2007; 134(3): 565 - 573. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nishiyama, S. Miyoshi, N. Hida, T. Uyama, K. Okamoto, Y. Ikegami, K. Miyado, K. Segawa, M. Terai, M. Sakamoto, et al. The Significant Cardiomyogenic Potential of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells In Vitro Stem Cells, August 1, 2007; 25(8): 2017 - 2024. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Coppi, A. M. Pugliese, S. Urbani, A. Melani, E. Cerbai, B. Mazzanti, A. Bosi, R. Saccardi, and F. Pedata ATP Modulates Cell Proliferation and Elicits Two Different Electrophysiological Responses in Human Mesenchymal Stem Cells Stem Cells, July 1, 2007; 25(7): 1840 - 1849. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Pevsner-Fischer, V. Morad, M. Cohen-Sfady, L. Rousso-Noori, A. Zanin-Zhorov, S. Cohen, I. R. Cohen, and D. Zipori Toll-like receptors and their ligands control mesenchymal stem cell functions Blood, February 15, 2007; 109(4): 1422 - 1432. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. C. Amado, K. H. Schuleri, A. P. Saliaris, A. J. Boyle, R. Helm, B. Oskouei, M. Centola, V. Eneboe, R. Young, J. A.C. Lima, et al. Multimodality Noninvasive Imaging Demonstrates In Vivo Cardiac Regeneration After Mesenchymal Stem Cell Therapy J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2116 - 2124. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Rosen Are Stem Cells Drugs?: The Regulation of Stem Cell Research and Development Circulation, October 31, 2006; 114(18): 1992 - 2000. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Boyle, S. P. Schulman, and J. M. Hare Stem Cell Therapy for Cardiac Repair: Ready for the Next Step Circulation, July 25, 2006; 114(4): 339 - 352. [Full Text] [PDF] |
||||
![]() |
M. F. Berry, A. J. Engler, Y. J. Woo, T. J. Pirolli, L. T. Bish, V. Jayasankar, K. J. Morine, T. J. Gardner, D. E. Discher, and H. L. Sweeney Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2196 - H2203. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Y. Khakoo, S. Pati, S. A. Anderson, W. Reid, M. F. Elshal, I. I. Rovira, A. T. Nguyen, D. Malide, C. A. Combs, G. Hall, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma J. Exp. Med., May 15, 2006; 203(5): 1235 - 1247. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Freyman, G. Polin, H. Osman, J. Crary, M. Lu, L. Cheng, M. Palasis, and R. L. Wilensky A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction Eur. Heart J., May 1, 2006; 27(9): 1114 - 1122. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Kern, H. Eichler, J. Stoeve, H. Kluter, and K. Bieback Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue Stem Cells, May 1, 2006; 24(5): 1294 - 1301. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Gnecchi, H. He, N. Noiseux, O. D. Liang, L. Zhang, F. Morello, H. Mu, L. G. Melo, R. E. Pratt, J. S. Ingwall, et al. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement FASEB J, April 1, 2006; 20(6): 661 - 669. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Francois, M. Bensidhoum, M. Mouiseddine, C. Mazurier, B. Allenet, A. Semont, J. Frick, A. Sache, S. Bouchet, D. Thierry, et al. Local Irradiation Not Only Induces Homing of Human Mesenchymal Stem Cells at Exposed Sites but Promotes Their Widespread Engraftment to Multiple Organs: A Study of Their Quantitative Distribution After Irradiation Damage Stem Cells, April 1, 2006; 24(4): 1020 - 1029. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. P. Raikwar, T. Mueller, and N. Zavazava Strategies for Developing Therapeutic Application of Human Embryonic Stem Cells Physiology, February 1, 2006; 21(1): 19 - 28. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Zhu, J. Chen, X. Cong, S. Hu, and X. Chen Hypoxia and Serum Deprivation-Induced Apoptosis in Mesenchymal Stem Cells Stem Cells, February 1, 2006; 24(2): 416 - 425. [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] |
||||
![]() |
N. Eliopoulos, J. Stagg, L. Lejeune, S. Pommey, and J. Galipeau Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice Blood, December 15, 2005; 106(13): 4057 - 4065. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Dimarakis, N. A. Habib, and M. Y.A. Gordon Adult bone marrow-derived stem cells and the injured heart: just the beginning? Eur. J. Cardiothorac. Surg., November 1, 2005; 28(5): 665 - 676. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sartore, M. Lenzi, A. Angelini, A. Chiavegato, L. Gasparotto, P. D. Coppi, R. Bianco, and G. Gerosa Amniotic mesenchymal cells autotransplanted in a porcine model of cardiac ischemia do not differentiate to cardiogenic phenotypes Eur. J. Cardiothorac. Surg., November 1, 2005; 28(5): 677 - 684. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. R. Makkar, M. J. Price, M. Lill, M. Frantzen, K. Takizawa, T. Kleisli, J. Zheng, S. Kar, R. McClelan, T. Miyamota, et al. Intramyocardial Injection of Allogenic Bone Marrow-Derived Mesenchymal Stem Cells Without Immunosuppression Preserves Cardiac Function in a Porcine Model of Myocardial Infarction Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2005; 10(4): 225 - 233. [Abstract] [PDF] |
||||
![]() |
A. Leri, J. Kajstura, and P. Anversa Cardiac Stem Cells and Mechanisms of Myocardial Regeneration Physiol Rev, October 1, 2005; 85(4): 1373 - 1416. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Kraitchman, M. Tatsumi, W. D. Gilson, T. Ishimori, D. Kedziorek, P. Walczak, W. P. Segars, H. H. Chen, D. Fritzges, I. Izbudak, et al. Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction Circulation, September 6, 2005; 112(10): 1451 - 1461. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Laflamme, J. Gold, C. Xu, M. Hassanipour, E. Rosler, S. Police, V. Muskheli, and C. E. Murry Formation of Human Myocardium in the Rat Heart from Human Embryonic Stem Cells Am. J. Pathol., September 1, 2005; 167(3): 663 - 671. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-O. Kim, H. Tian, K. Prasongsukarn, J. Wu, D. Angoulvant, S. Wnendt, A. Muhs, D. Spitkovsky, and R.-K. Li Cell Transplantation Improves Ventricular Function After a Myocardial Infarction: A Preclinical Study of Human Unrestricted Somatic Stem Cells in a Porcine Model Circulation, August 30, 2005; 112(9_suppl): I-96 - I-104. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nagaya, K. Kangawa, T. Itoh, T. Iwase, S. Murakami, Y. Miyahara, T. Fujii, M. Uematsu, H. Ohgushi, M. Yamagishi, et al. Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy Circulation, August 23, 2005; 112(8): 1128 - 1135. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. C. Amado, A. P. Saliaris, K. H. Schuleri, M. St. John, J.-S. Xie, S. Cattaneo, D. J. Durand, T. Fitton, J. Q. Kuang, G. Stewart, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction PNAS, August 9, 2005; 102(32): 11474 - 11479. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Dow, B. Z. Simkhovich, L. Kedes, and R. A. Kloner Washout of transplanted cells from the heart: A potential new hurdle for cell transplantation therapy Cardiovasc Res, August 1, 2005; 67(2): 301 - 307. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Sordi, M. L. Malosio, F. Marchesi, A. Mercalli, R. Melzi, T. Giordano, N. Belmonte, G. Ferrari, B. E. Leone, F. Bertuzzi, et al. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets Blood, July 15, 2005; 106(2): 419 - 427. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. C. Wollert and H. Drexler Mesenchymal Stem Cells for Myocardial Infarction: Promises and Pitfalls Circulation, July 12, 2005; 112(2): 151 - 153. [Full Text] [PDF] |
||||
![]() |
Y. L. Tang, Q. Zhao, X. Qin, L. Shen, L. Cheng, J. Ge, and M. I. Phillips Paracrine Action Enhances the Effects of Autologous Mesenchymal Stem Cell Transplantation on Vascular Regeneration in Rat Model of Myocardial Infarction Ann. Thorac. Surg., July 1, 2005; 80(1): 229 - 237. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Azarnoush, A. Maurel, L. Sebbah, C. Carrion, A. Bissery, C. Mandet, J. Pouly, P. Bruneval, A. A. Hagege, and P. Menasche Enhancement of the functional benefits of skeletal myoblast transplantation by means of coadministration of hypoxia-inducible factor 1{alpha} J. Thorac. Cardiovasc. Surg., July 1, 2005; 130(1): 173 - 179. [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] |
||||
![]() |
R. Matsumoto, T. Omura, M. Yoshiyama, T. Hayashi, S. Inamoto, K.-R. Koh, K. Ohta, Y. Izumi, Y. Nakamura, K. Akioka, et al. Vascular Endothelial Growth Factor-Expressing Mesenchymal Stem Cell Transplantation for the Treatment of Acute Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1168 - 1173. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Kofidis, J. L. de Bruin, T. Yamane, M. Tanaka, D. R. Lebl, R.-J. Swijnenburg, I. L. Weissman, and R. C. Robbins Stimulation of Paracrine Pathways With Growth Factors Enhances Embryonic Stem Cell Engraftment and Host-Specific Differentiation in the Heart After Ischemic Myocardial Injury Circulation, May 17, 2005; 111(19): 2486 - 2493. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.-R. Li, H. Sun, X. Deng, and C.-P. Lau Characterization of Ionic Currents in Human Mesenchymal Stem Cells from Bone Marrow Stem Cells, March 1, 2005; 23(3): 371 - 382. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Aggarwal and M. F. Pittenger Human mesenchymal stem cells modulate allogeneic immune cell responses Blood, February 15, 2005; 105(4): 1815 - 1822. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. C. Wollert and H. Drexler Clinical Applications of Stem Cells for the Heart Circ. Res., February 4, 2005; 96(2): 151 - 163. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Dawn and R. Bolli Bone marrow cells for cardiac regeneration: the quest for the protagonist continues Cardiovasc Res, February 1, 2005; 65(2): 293 - 295. [Full Text] [PDF] |
||||
![]() |
S. Davani, F. Deschaseaux, D. Chalmers, P. Tiberghien, and J.-P. Kantelip Can stem cells mend a broken heart? Cardiovasc Res, February 1, 2005; 65(2): 305 - 316. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. V. Silva, S. Litovsky, J. A.R. Assad, A. L.S. Sousa, B. J. Martin, D. Vela, S. C. Coulter, J. Lin, J. Ober, W. K. Vaughn, et al. Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Enhance Vascular Density, and Improve Heart Function in a Canine Chronic Ischemia Model Circulation, January 18, 2005; 111(2): 150 - 156. [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] |
||||
![]() |
M. Kucia, B. Dawn, G. Hunt, Y. Guo, M. Wysoczynski, M. Majka, J. Ratajczak, F. Rezzoug, S. T. Ildstad, R. Bolli, et al. Cells Expressing Early Cardiac Markers Reside in the Bone Marrow and Are Mobilized Into the Pe |