Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease.

Abstract

Chagasic cardiomyopathy, resulting from infection with the parasite Trypanosoma cruzi, was discovered more than a century ago and remains an incurable disease. Due to the unique properties of mesenchymal stem cells (MSC) we hypothesized that these cells could have therapeutic potential for chagasic cardiomyopathy. Recently, our group pioneered use of nanoparticle-labeled MSC to correlate migration with its effect in an acute Chagas disease model. We expanded our investigation into a chronic model and performed more comprehensive assays. Infected mice were treated with nanoparticle-labeled MSC and their migration was correlated with alterations in heart morphology, metalloproteinase activity, and expression of several proteins. The vast majority of labeled MSC migrated to liver, lungs and spleen whereas a small number of cells migrated to chagasic hearts. Magnetic resonance imaging demonstrated that MSC therapy reduced heart dilatation. Additionally metalloproteinase activity was higher in heart and other organs of infected mice. Protein expression analyses revealed that connexin 43, laminin γ1, IL-10 and INF-γ were affected by the disease and recovered after cell therapy. Interestingly, MSC therapy led to upregulation of SDF-1 and c-kit in the hearts. The beneficial effect of MSC therapy in Chagas disease is likely due to an indirect action of the cells of the heart, rather than the incorporation of large numbers of stem cells into working myocardium.

• Authors: Jasmin, Linda A Jelicks, Herbert B Tanowitz, Vera Maria Peters, Rosalia Mendez-Otero, Antonio C Campos de Carvalho, David C Spray
• Journal: Microbes and infection (Microbes Infect) Vol. 16 Issue 11 Pg. 923-935 (Nov 2014) ISSN: 1769-714X [Electronic] France
• PMID: 25218054 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier Masson SAS.

Chemical References

• Chemokine CXCL12
• Cxcl12 protein, mouse
• Cytokines
• Proto-Oncogene Proteins c-kit

Topics

• Animals
• Bone Marrow Transplantation (methods)
• Chagas Disease (pathology, therapy)
• Chemokine CXCL12 (analysis)
• Cytokines (blood)
• Disease Models, Animal
• Heart (diagnostic imaging)
• Magnetic Resonance Imaging
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mice
• Molecular Imaging
• Myocardium (pathology)
• Proto-Oncogene Proteins c-kit (analysis)
• Radiography
• Treatment Outcome