Published Online
on July 18, 2005

A more recent version of this article appeared on July 26, 2005

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Submitted on March 31, 2004
Revised on January 28, 2005
Accepted on February 23, 2005

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, and 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.

^* To whom correspondence should be addressed. E-mail: diretoria.cientifica{at}procardiaco.com.br.

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

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