Transendocardial autologous bone marrow mononuclear cell injection in ischemic heart failure: postmortem anatomicopathologic and immunohistochemical findings.
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.


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 alpha-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.
Dohmann
Hans F R
HF
Hospital Procardiaco, Rio de Janeiro, Brazil. diretoria.cientifica@procardiaco.com.br
Perin
Emerson C
EC
Takiya
Christina M
CM
Silva
Guilherme V
GV
Silva
Suzana A
SA
Sousa
Andre L S
AL
Mesquita
Claudio T
CT
Rossi
Maria-Isabel D
MI
Pascarelli
Bernardo M O
BM
Assis
Isabella M
IM
Dutra
Helio S
HS
Assad
João A R
JA
Castello-Branco
Rodrigo V
RV
Drummond
Cantidio
C
Dohmann
Hans J F
HJ
Willerson
James T
JT
Borojevic
Radovan
R
D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D003893:Desmin / Q000032:analysis; D006333:Heart Failure / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D015899:Tomography, Emission-Computed, Single-Photon; D014182:Transplantation, Autologous
D003893:Desmin