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(Circulation. 2006;114:2163-2169.)
© 2006 American Heart Association, Inc.

Molecular Cardiology

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; 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.).

Correspondence to Takayuki Asahara, MD, Laboratory for Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation, 2–2 Minatojima-Minamimachi, Chuo-Ku, Kobe, 650–0047, Japan (e-mail asa777{at}aol.com); or Douglas W. Losordo, MD, Division of Cardiovascular Research, St Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA 02135 (e-mail douglas.losordo@tufts.edu).

Received March 3, 2006; de novo received June 8, 2006; revision received August 23, 2006; accepted September 8, 2006.

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.

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