on August 4, 2003
Circulation. 2003
Published online before print August 4, 2003, doi: 10.1161/01.CIR.0000084828.50310.6A
Published online before print August 4, 2003, doi: 10.1161/01.CIR.0000084828.50310.6A
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 10, 2003
From the Neufeld Cardiac Research Institute (I.M.B.,
P.C., J.B., M.S.F., S.E., A.T., L.M., J.L.) and Danek Gertner Institute
of Human Genetics (E.G.), Sheba Medical Center, Tel-Hashomer, Israel;
Department of Molecular Cell Biology (D.Z.), Weizmann Institute of
Science, Rehovot, Israel; Institute for Genetic Medicine (L.H.K.,
R.A.K.), Department of Biochemistry & Molecular Biology, Los Angeles,
Calif; Department of Medicine (L.H.K.), Keck School of Medicine of the
University of Southern California, Los Angeles, Calif; and Heart
Institute (R.A.K.), Good Samaritan Hospital, Los Angeles,
Calif. * To whom correspondence should be addressed. E-mail: leorj{at}post.tau.ac.il.
Background--Systemic delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI). Methods and Results--BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-labeled cells (4x106) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the 99mTc-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in the heart, and specifically higher uptake in infarcted compared with sham-MI hearts. Histological examination at 1 week after infusion identified labeled cells either in the infarcted or border zone but not in remote viable myocardium or sham-MI hearts. Labeled cells were also identified in the lung, liver, spleen, and bone marrow. Conclusions--Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs. Direct left ventricular cavity infusion enhances migration and colonization of the cells preferentially to the ischemic myocardium.
Revised on April 17, 2003
Accepted on April 25, 2003
Systemic Delivery of Bone Marrow-Derived
Mesenchymal Stem Cells to the Infarcted
Myocardium. Feasibility, Cell Migration, and Body
Distribution
Israel M. Barbash MD,
Key words: cells • myocardial infarction • nuclear medicine • transplantation
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 S. Morikawa, Y. Mabuchi, Y. Kubota, Y. Nagai, K. Niibe, E. Hiratsu, S. Suzuki, C. Miyauchi-Hara, N. Nagoshi, T. Sunabori, et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow J. Exp. Med., October 26, 2009; 206(11): 2483 - 2496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Gersh, R. D. Simari, A. Behfar, C. M. Terzic, and A. Terzic Cardiac Cell Repair Therapy: A Clinical Perspective Mayo Clin. Proc., October 1, 2009; 84(10): 876 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.T.-J. Huang, S. Gronthos, and S. Shi Mesenchymal Stem Cells Derived from Dental Tissues vs. Those from Other Sources: Their Biology and Role in Regenerative Medicine Journal of Dental Research, September 1, 2009; 88(9): 792 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Belmadani, K. Matrougui, C. Kolz, Y. F. Pung, D. Palen, D. J. Prockop, and W. M. Chilian Amplification of Coronary Arteriogenic Capacity of Multipotent Stromal Cells by Epidermal Growth Factor Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 802 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shabbir, D. Zisa, G. Suzuki, and T. Lee Heart failure therapy mediated by the trophic activities of bone marrow mesenchymal stem cells: a noninvasive therapeutic regimen Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1888 - H1897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. U. Schraufstatter, R. G. DiScipio, M. Zhao, and S. K. Khaldoyanidi C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation J. Immunol., March 15, 2009; 182(6): 3827 - 3836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Bagi and G. Kaley Where Have All the Stem Cells Gone? Circ. Res., February 13, 2009; 104(3): 280 - 281. [Full Text] [PDF]
|
|
|
|
|
|
C. Toma, W. R. Wagner, S. Bowry, A. Schwartz, and F. Villanueva Fate Of Culture-Expanded Mesenchymal Stem Cells in The Microvasculature: In Vivo Observations of Cell Kinetics Circ. Res., February 13, 2009; 104(3): 398 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Vela, G. V. Silva, J. A.R. Assad, A. L.S. Sousa, S. Coulter, M. R. Fernandes, E. C. Perin, J. T. Willerson, and L. M. Buja Histopathological Study of Healing After Allogenic Mesenchymal Stem Cell Delivery in Myocardial Infarction in Dogs J. Histochem. Cytochem., February 1, 2009; 57(2): 167 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Walker, S. K. Shah, M. T. Harting, and C. S. Cox Jr Progenitor cell therapies for traumatic brain injury: barriers and opportunities in translation Dis. Model. Mech., January 1, 2009; 2(1-2): 23 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kyriakou, N. Rabin, A. Pizzey, A. Nathwani, and K. Yong Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model Haematologica, October 1, 2008; 93(10): 1457 - 1465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Casiraghi, N. Azzollini, P. Cassis, B. Imberti, M. Morigi, D. Cugini, R. A. Cavinato, M. Todeschini, S. Solini, A. Sonzogni, et al. Pretransplant Infusion of Mesenchymal Stem Cells Prolongs the Survival of a Semiallogeneic Heart Transplant through the Generation of Regulatory T Cells J. Immunol., September 15, 2008; 181(6): 3933 - 3946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Yang, H.-Y. Qian, J. Huang, Y.-J. Geng, R.-L. Gao, K.-F. Dou, G.-S. Yang, J.-J. Li, R. Shen, Z.-X. He, et al. Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts Eur. Heart J., June 2, 2008; 29(12): 1578 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Potapova, P. R. Brink, I. S. Cohen, and S. V. Doronin Culturing of Human Mesenchymal Stem Cells as Three-dimensional Aggregates Induces Functional Expression of CXCR4 That Regulates Adhesion to Endothelial Cells J. Biol. Chem., May 9, 2008; 283(19): 13100 - 13107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Jones and D. McGonagle Human bone marrow mesenchymal stem cells in vivo Rheumatology, February 1, 2008; 47(2): 126 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Wang, W.-J. Cherng, N.-I Yang, L.-T. Kuo, C.-M. Hsu, H.-I Yeh, Y.-J. Lan, C.-H. Yeh, and W. L. Stanford Late-Outgrowth Endothelial Cells Attenuate Intimal Hyperplasia Contributed by Mesenchymal Stem Cells After Vascular Injury Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 54 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Zhang and J. C. Wu Comparison of Imaging Techniques for Tracking Cardiac Stem Cell Therapy J. Nucl. Med., December 1, 2007; 48(12): 1916 - 1919. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, P. Song, Y. Tang, X.-l. Zhang, S.-h. Zhao, Y.-j. Wei, and S.-s. Hu Injection of bone marrow mesenchymal stem cells in the borderline area of infarcted myocardium: heart status and cell distribution. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1234 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tongers and D. W. Losordo Frontiers in Nephrology: The Evolving Therapeutic Applications of Endothelial Progenitor Cells J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2843 - 2852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Amsalem, Y. Mardor, M. S. Feinberg, N. Landa, L. Miller, D. Daniels, A. Ocherashvilli, R. Holbova, O. Yosef, I. M. Barbash, et al. Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium Circulation, September 11, 2007; 116(11_suppl): I-38 - I-45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.M. Dwyer, S.M. Potter-Beirne, K.A. Harrington, A.J. Lowery, E. Hennessy, J.M. Murphy, F.P. Barry, T. O'Brien, and M.J. Kerin Monocyte Chemotactic Protein-1 Secreted by Primary Breast Tumors Stimulates Migration of Mesenchymal Stem Cells Clin. Cancer Res., September 1, 2007; 13(17): 5020 - 5027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gupta, X. Su, B. Popov, J. W. Lee, V. Serikov, and M. A. Matthay Intrapulmonary Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Survival and Attenuates Endotoxin-Induced Acute Lung Injury in Mice J. Immunol., August 1, 2007; 179(3): 1855 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Aupperle, J. Garbade, A. Schubert, M. Barten, S. Dhein, H.-A Schoon, and F.-W Mohr Effects of Autologous Stem Cells on Immunohistochemical Patterns and Gene Expression of Metalloproteinases and Their Tissue Inhibitors in Doxorubicin Cardiomyopathy in a Rabbit Model Vet. Pathol., July 1, 2007; 44(4): 494 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Penicka, O Lang, P Widimsky, P Kobylka, T Kozak, T Vanek, J Dvorak, J Tintera, and J Bartunek One-day kinetics of myocardial engraftment after intracoronary injection of bone marrow mononuclear cells in patients with acute and chronic myocardial infarction Heart, July 1, 2007; 93(7): 837 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Saeed, D. Saloner, A. Martin, L. Do, O. Weber, P. C. Ursell, A. Jacquier, R. Lee, and C. B. Higgins Adeno-associated Viral Vector-Encoding Vascular Endothelial Growth Factor Gene: Effect on Cardiovascular MR Perfusion and Infarct Resorption Measurements in Swine Radiology, May 1, 2007; 243(2): 451 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L.M.A. Beeres, F. M. Bengel, J. Bartunek, D. E. Atsma, J. M. Hill, M. Vanderheyden, M. Penicka, M. J. Schalij, W. Wijns, and J. J. Bax Role of Imaging in Cardiac Stem Cell Therapy J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1137 - 1148. [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]
|
|
|
|
|
|
R. Zhou, P. D. Acton, and V. A. Ferrari Imaging Stem Cells Implanted in Infarcted Myocardium J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2094 - 2106. [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]
|
|
|
|
|
|
W. J. Kang, H.-J. Kang, H.-S. Kim, J.-K. Chung, M. C. Lee, and D. S. Lee Tissue Distribution of 18F-FDG-Labeled Peripheral Hematopoietic Stem Cells After Intracoronary Administration in Patients with Myocardial Infarction J. Nucl. Med., August 1, 2006; 47(8): 1295 - 1301. [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]
|
|
|
|
|
|
J.-Y. Min, X. Huang, M. Xiang, A. Meissner, Y. Chen, Q. Ke, E. Kaplan, J. S. Rana, P. Oettgen, and J. P. Morgan Homing of intravenously infused embryonic stem cell-derived cells to injured hearts after myocardial infarction J. Thorac. Cardiovasc. Surg., April 1, 2006; 131(4): 889 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. F. M. Segers, I. Van Riet, L. J. Andries, K. Lemmens, M. J. Demolder, A. J. M. L. De Becker, M. M. Kockx, and G. W. De Keulenaer Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1370 - H1377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Misao, G. Takemura, M. Arai, S. Sato, K. Suzuki, S. Miyata, K.-i. Kosai, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Bone marrow-derived myocyte-like cells and regulation of repair-related cytokines after bone marrow cell transplantation Cardiovasc Res, February 1, 2006; 69(2): 476 - 490. [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]
|
|
|
|
|
|
H. Ince, M. Petzsch, H. D. Kleine, H. Schmidt, T. Rehders, T. Korber, C. Schumichen, M. Freund, and C. A. Nienaber Preservation From Left Ventricular Remodeling by Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Use of Granulocyte-Colony-Stimulating Factor (FIRSTLINE-AMI) Circulation, November 15, 2005; 112(20): 3097 - 3106. [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]
|
|
|
|
|
|
H. Ince, M. Petzsch, H. D. Kleine, H. Eckard, T. Rehders, D. Burska, S. Kische, M. Freund, and C. A. Nienaber Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction: Final 1-year Results of the Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Granulocyte Colony-Stimulating Factor (FIRSTLINE-AMI) Trial Circulation, August 30, 2005; 112(9_suppl): I-73 - I-80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Siepe, C. Heilmann, P. von Samson, P. Menasche, and F. Beyersdorf Stem cell research and cell transplantation for myocardial regeneration Eur. J. Cardiothorac. Surg., August 1, 2005; 28(2): 318 - 324. [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]
|
|
|
|
|
|
J. H. Kang, D. S. Lee, J. C. Paeng, J. S. Lee, Y. H. Kim, Y. J. Lee, D. W. Hwang, J. M. Jeong, S. M. Lim, J.-K. Chung, et al. Development of a Sodium/Iodide Symporter (NIS)-Transgenic Mouse for Imaging of Cardiomyocyte-Specific Reporter Gene Expression J. Nucl. Med., March 1, 2005; 46(3): 479 - 483. [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]
|
|
|
|
|
|
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 Peripheral Blood After Myocardial Infarction Circ. Res., December 10, 2004; 95(12): 1191 - 1199. [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]
|
|
|
|
|
|
H. Kawada, J. Fujita, K. Kinjo, Y. Matsuzaki, M. Tsuma, H. Miyatake, Y. Muguruma, K. Tsuboi, Y. Itabashi, Y. Ikeda, et al. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction Blood, December 1, 2004; 104(12): 3581 - 3587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. V. Frangioni and R. J. Hajjar In Vivo Tracking of Stem Cells for Clinical Trials in Cardiovascular Disease Circulation, November 23, 2004; 110(21): 3378 - 3383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Anjos-Afonso, E. K. Siapati, and D. Bonnet In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions J. Cell Sci., November 1, 2004; 117(23): 5655 - 5664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Pittenger and B. J. Martin Mesenchymal Stem Cells and Their Potential as Cardiac Therapeutics Circ. Res., July 9, 2004; 95(1): 9 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-S. Tsai, J.-L. Lee, Y.-J. Chang, and S.-M. Hwang Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol Hum. Reprod., June 1, 2004; 19(6): 1450 - 1456. [Abstract] [Full Text] [PDF]
|
|