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(Circulation. 2006;114:I-120 – I-124.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Simultaneous Autologous Transplantation of Cocultured Mesenchymal Stem Cells and Skeletal Myoblasts Improves Ventricular Function in a Murine Model of Chagas Disease

L.C. Guarita-Souza, MD, PhD; K.A.T. Carvalho, MD; V. Woitowicz, MD; C. Rebelatto, BSc; A. Senegaglia, BSc; P. Hansen, BSc; N. Miyague, MD, PhD; J.C. Francisco, BSc; M. Olandoski, BSc; J.R. Faria-Neto, MD, PhD; P. Brofman, MD, PhD

From Experimental Laboratory of Cell Culture Institute of Biological and Health Sciences. Pontificia Universidade Catolica do Paraná (PUCPR), Brazil.

Correspondence to Luis César Guarita Souza, Rua Silveira Peixoto, 1062, ap 162, CEP: 80240-120, Curitiba (Pr), Brazil. E-mail llccggss{at}hotmail.com

Background— Cellular transplantation is emerging as a promising strategy for the treatment of postinfarction ventricular dysfunction. Whether its beneficial effects can be extended to other cardiomyopathies remains an unexplored question. We evaluated the histological and functional effects of simultaneous autologous transplantation of co-cultured stem cells and skeletal myoblasts in an experimental model of dilated cardiomyopathy caused by Chagas disease, characterized by diffuse fibrosis and impairment of microcirculation.

Methods and Results— Wistar rats weighing 200 grams were infected intraperitoneally with 15x10⁴ trypomastigotes. After 8 months, 2-dimensional echocardiographic study was performed for baseline assessment of left ventricle (LV) ejection fraction (EF) (%), left ventricle end-diastolic volume (LVEDV) (mL), and left ventricle end-systolic volume (LVESV) (mL). Animals with LV dysfunction (EF <37%) were selected for the study. Autologous skeletal myoblasts were isolated from muscle biopsy and mesenchymal stem cells from bone marrow aspirates were co-cultured in vitro for 14 days, yielding a cell viability of >90%. Eleven animals received autologous transplant of 5.4x10⁶±8.0x10⁶ cells (300 µL) into the LV wall. The control group (n=10) received culture medium (300 µL). Cell types were identified with vimentin and fast myosin. After 4 weeks, ventricular function was reassessed by echo. For histological analysis, heart tissue was stained with hematoxylin and eosin and immunostained for fast myosin. After 4 weeks, cell transplantation significantly improved EF and reduced LVEDV and LVESV. No change was observed in the control group.

Conclusion— The co-transplant of stem cells and skeletal myoblasts is functionally effective in the Chagas disease ventricular dysfunction.

Key Words: cells • Chagas disease • heart failure • transplantation