Published Online
on October 30, 2006

A more recent version of this article appeared on November 14, 2006

This Article Full Text (PDF) All Versions of this Article: 114/20/2163    most recent CIRCULATIONAHA.106.644518v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawamoto, A. Articles by Losordo, D. W. Search for Related Content PubMed PubMed Citation Articles by Kawamoto, A. Articles by Losordo, D. W. Related Collections Angiogenesis Transplantation Acute myocardial infarction Endothelium/vascular type/nitric oxide

Submitted on March 3, 2006
Revised on August 23, 2006
Accepted on September 8, 2006

CD34-Positive Cells Exhibit Increased Potency and Safety for Therapeutic Neovascularization After Myocardial Infarction Compared With Total Mononuclear Cells

Atsuhiko Kawamoto MD, PhD, Hiroto Iwasaki MD, Kengo Kusano MD, PhD, Toshinori Murayama MD, PhD, Akira Oyamada BS, Marcy Silver BS, Christine Hulbert BS, Mary Gavin BS, Allison Hanley BS, Hong Ma BS, Marianne Kearney BS, Victor Zak PhD, Takayuki Asahara MD, PhD^*, and Douglas W. Losordo MD

From the Division of Cardiovascular Research, St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass (A.K., K.K., T.M., M.S., C.H., M.G., A.H., H.M., M.K., V.Z., T.A., D.W.L.); Laboratory for Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation/RIKEN Center for Developmental Biology, Kobe, Japan (A.K., H.I., A.O., T.A.); and Department of Regeneration Medicine Science, Tokai University School of Medicine, Isehara, Japan (T.A.).

^* To whom correspondence should be addressed. E-mail: asa777{at}aol.com.

Background--We compared the therapeutic potential of purified mobilized human CD34⁺ cells with that of mobilized total mononuclear cells (tMNCs) for the preservation/recovery of myocardial tissue integrity and function after myocardial infarction (MI).

Methods and Results--CD34⁺ cells were purified from peripheral blood tMNCs of healthy volunteers by magnetic cell sorting after a 5-day administration of granulocyte colony-stimulating factor. Phosphate-buffered saline (PBS), 5x10⁵ CD34⁺ cells/kg, 5x10⁵ tMNCs/kg (low-dose MNCs [loMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5x10⁵ CD34⁺ cells/kg was transplanted intramyocardially 10 minutes after the induction of MI in athymic nude rats. Hematoxylin and eosin staining revealed that moderate to severe hemorrhagic MI on day 3 was more frequent in the hiMNC group than in the PBS and CD34⁺ cell groups. Immunostaining for human-specific CD45 revealed abundant distribution of hematopoietic/inflammatory cells derived from transplanted cells in the ischemic myocardium of the hiMNC group. Capillary density on day 28 was significantly greater in the CD34⁺ cell group (721.1±19.9 per 1 mm²) than in the PBS, loMNC, and hiMNC groups (384.7±11.0, 372.5±14.1, and 497.5±24.0 per 1 mm²) (P<0.01). Percent fibrosis area on day 28 was less in the CD34⁺ cell group (15.6±0.9%) than in the PBS, loMNC, and hiMNC groups (26.3±1.2%, 27.5±1.8%, and 22.2±1.8%) (P<0.05). Echocardiographic fractional shortening on day 28 was significantly higher in the CD34⁺ cell group (30.3±0.9%) than in the PBS, loMNC, and hiMNC groups (22.7±1.5%, 23.4±1.1%, and 24.9±1.7%; P<0.05). Echocardiographic regional wall motion score was better preserved in the CD34⁺ cell group (21.8±0.5) than in the PBS, loMNC, and hiMNC groups (25.4±0.4, 24.9±0.4, and 24.1±0.6; P<0.05).

Conclusions--CD34⁺ cells exhibit superior efficacy for preserving myocardial integrity and function after MI than unselected circulating MNCs.

Key words: angiogenesis • endothelium • ischemia • progenitor cells • stem cells

This article has been cited by other articles:

				Y. Mifune, T. Matsumoto, A. Kawamoto, R. Kuroda, T. Shoji, H. Iwasaki, S.-M. Kwon, M. Miwa, M. Kurosaka, and T. Asahara Local Delivery of Granulocyte Colony Stimulating Factor-Mobilized CD34-Positive Progenitor Cells Using Bioscaffold for Modality of Unhealing Bone Fracture Stem Cells, June 1, 2008; 26(6): 1395 - 1405. [Abstract] [Full Text] [PDF]

				B. Dawn, S. Tiwari, M. J. Kucia, E. K. Zuba-Surma, Y. Guo, S. K. SanganalMath, A. Abdel-Latif, G. Hunt, R. J. Vincent, H. Taher, et al. Transplantation of Bone Marrow-Derived Very Small Embryonic-Like Stem Cells Attenuates Left Ventricular Dysfunction and Remodeling After Myocardial Infarction Stem Cells, June 1, 2008; 26(6): 1646 - 1655. [Abstract] [Full Text] [PDF]

				C Kalka and I. Baumgartner Gene and stem cell therapy in peripheral arterial occlusive disease Vascular Medicine, May 1, 2008; 13(2): 157 - 172. [Abstract] [PDF]

				K. Tei, T. Matsumoto, Y. Mifune, K. Ishida, K. Sasaki, T. Shoji, S. Kubo, A. Kawamoto, T. Asahara, M. Kurosaka, et al. Administrations of Peripheral Blood CD34-Positive Cells Contribute to Medial Collateral Ligament Healing via Vasculogenesis Stem Cells, March 1, 2008; 26(3): 819 - 830. [Abstract] [Full Text] [PDF]

				M.-M. Zaruba, B. C. Huber, S. Brunner, E. Deindl, R. David, R. Fischer, G. Assmann, N. Herbach, S. Grundmann, R. Wanke, et al. Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival Cardiovasc Res, March 1, 2008; 77(4): 722 - 731. [Abstract] [Full Text] [PDF]

				M. Rota, J. Kajstura, T. Hosoda, C. Bearzi, S. Vitale, G. Esposito, G. Iaffaldano, M. E. Padin-Iruegas, A. Gonzalez, R. Rizzi, et al. Bone marrow cells adopt the cardiomyogenic fate in vivo PNAS, November 6, 2007; 104(45): 17783 - 17788. [Abstract] [Full Text] [PDF]

				T.-S. Li, M. Murakami, T. Kobayashi, B. Shirasawa, A. Mikamo, and K. Hamano Long-term efficacy and safety of the intramyocardial implantation of autologous bone marrow cells for the treatment of ischemic heart disease. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1347 - 1349. [Full Text] [PDF]

				A. M. Zeiher, V. Schachinger, S. Dimmeler, and For the REPAIR-AMI Investigators Improved clinical outcome after intracoronary administration of bone marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial: reply Eur. Heart J., September 1, 2007; 28(17): 2173 - 2174. [Full Text] [PDF]

				D. W. Losordo, R. A. Schatz, C. J. White, J. E. Udelson, V. Veereshwarayya, M. Durgin, K. K. Poh, R. Weinstein, M. Kearney, M. Chaudhry, et al. Intramyocardial Transplantation of Autologous CD34+ Stem Cells for Intractable Angina: A Phase I/IIa Double-Blind, Randomized Controlled Trial Circulation, June 26, 2007; 115(25): 3165 - 3172. [Abstract] [Full Text] [PDF]

				P. Anversa, J. Kajstura, and A. Leri If I Can Stop One Heart From Breaking Circulation, February 20, 2007; 115(7): 829 - 832. [Full Text] [PDF]