This Article Full Text Full Text (PDF) All Versions of this Article: 112/4/521    most recent CIRCULATIONAHA.104.499178v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Dohmann, H. F.R. Articles by Borojevic, R. Search for Related Content PubMed PubMed Citation Articles by Dohmann, H. F.R. Articles by Borojevic, R. Related Collections Other myocardial biology Angiogenesis Heart failure - basic studies Ischemic biology - basic studies Catheter-based coronary and valvular interventions: other Other Treatment Chronic ischemic heart disease Other Vascular biology

(Circulation. 2005;112:521-526.)
© 2005 American Heart Association, Inc.

Heart Failure

Transendocardial Autologous Bone Marrow Mononuclear Cell Injection in Ischemic Heart Failure

Postmortem Anatomicopathologic and Immunohistochemical Findings

Hans F.R. Dohmann, MD^*; Emerson C. Perin, MD, PhD^*; Christina M. Takiya, MD, PhD; Guilherme V. Silva, MD; Suzana A. Silva, MD; Andre L.S. Sousa, MD; Claudio T. Mesquita, MD, PhD; Maria-Isabel D. Rossi, PhD; Bernardo M.O. Pascarelli, MD; Isabella M. Assis, MD; Helio S. Dutra, PhD; João A.R. Assad, MD; Rodrigo V. Castello-Branco, MD; Cantidio Drummond, MD; Hans J.F. Dohmann, MD, PhD; James T. Willerson, MD; Radovan Borojevic, PhD

From the Hospital Procardiaco (H.F.R.D., S.A.S., A.L.S.S., C.T.M., J.A.R.A., R.V.C.B., C.D., H.J.F.D.), Rio de Janeiro, Brazil; the Texas Heart Institute at St. Luke’s Episcopal Hospital (E.C.P., G.V.S., J.T.W.), Houston, Tex; and the Institute of Biomedical Sciences and Clementino Fraga Filho Hospital, Federal University (C.M.T., M.-I.D.R., B.M.O.P., I.M.A., H.S.D., R.B.), Rio de Janeiro, Brazil.

Correspondence to Hans F.R. Dohmann, MD, Rua General Polidoro 192, 22080-000 Rio de Janeiro, Brazil (e-mail diretoria.cientifica{at}procardiaco.com.br), or Emerson C. Perin, MD, 6624 Fannin, Suite 2220, Houston TX 77030 (e-mail eperin@crescentb.net).

Received March 31, 2004; de novo received August 13, 2004; revision received January 28, 2005; accepted February 23, 2005.

Background— Cell-based therapies for treatment of ischemic heart disease are currently under investigation. We previously reported the results of a phase I trial of transendocardial injection of autologous bone marrow mononuclear (ABMM) cells in patients with end-stage ischemic heart disease. The current report focuses on postmortem cardiac findings from one of the treated patients, who died 11 months after cell therapy.

Methods and Results— Anatomicopathologic, morphometric, and immunocytochemical findings from the anterolateral ventricular wall (with cell therapy) were compared with findings from the interventricular septum (normal perfusion and no cell therapy) and from the inferoposterior ventricular wall (extensive scar tissue and no cell therapy). No signs of adverse events were found in the cell-injected areas. Capillary density was significantly higher (P<0.001) in the anterolateral wall than in the previously infarcted tissue in the posterior wall. The prominent vasculature of the anterolateral wall was associated with hyperplasia of pericytes, mural cells, and adventitia. Some of these cells had acquired cytoskeletal elements and contractile proteins (troponin, sarcomeric -actinin, actinin), as well as the morphology of cardiomyocytes, and appeared to have migrated toward adjacent bundles of cardiomyocytes.

Conclusions— Eleven months after treatment, morphological and immunocytochemical analysis of the sites of ABMM cell injection showed no abnormal cell growth or tissue lesions and suggested that an active process of angiogenesis was present in both the fibrotic cicatricial tissue and the adjacent cardiac muscle. Some of the pericytes had acquired the morphology of cardiomyocytes, suggesting long-term sequential regeneration of the cardiac vascular tree and muscle.

Key Words: angiogenesis • stem cells • heart failure • revascularization • ischemia

This article has been cited by other articles:

				D. J. Prockop and S. D. Olson Clinical trials with adult stem/progenitor cells for tissue repair: let's not overlook some essential precautions Blood, April 15, 2007; 109(8): 3147 - 3151. [Full Text] [PDF]

				S. Zhang, E. Shpall, J. T. Willerson, and E. T.H. Yeh Fusion of Human Hematopoietic Progenitor Cells and Murine Cardiomyocytes Is Mediated by {alpha}4{beta}1 Integrin/Vascular Cell Adhesion Molecule-1 Interaction Circ. Res., March 16, 2007; 100(5): 693 - 702. [Abstract] [Full Text] [PDF]

				R. R. Smith, L. Barile, H. C. Cho, M. K. Leppo, J. M. Hare, E. Messina, A. Giacomello, M. R. Abraham, and E. Marban Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens Circulation, February 20, 2007; 115(7): 896 - 908. [Abstract] [Full Text] [PDF]

				R. de Silva, L. F. Gutierrez, A. N. Raval, E. R. McVeigh, C. Ozturk, and R. J. Lederman X-Ray Fused With Magnetic Resonance Imaging (XFM) to Target Endomyocardial Injections: Validation in a Swine Model of Myocardial Infarction Circulation, November 28, 2006; 114(22): 2342 - 2350. [Abstract] [Full Text] [PDF]

				I. Ben-Dor, S. Fuchs, and R. Kornowski Potential Hazards and Technical Considerations Associated With Myocardial Cell Transplantation Protocols for Ischemic Myocardial Syndrome J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1519 - 1526. [Abstract] [Full Text] [PDF]

				W.H. W. Tang and G. S. Francis The Year in Heart Failure J. Am. Coll. Cardiol., December 6, 2005; 46(11): 2125 - 2133. [Full Text] [PDF]

				J. T. Willerson, E. T.H. Yeh, Y.-J. Geng, and E. C. Perin Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusions in Humans Circ. Res., October 14, 2005; 97(8): 735 - 736. [Full Text] [PDF]