Mesenchymal Bone Marrow Cell Therapy in a Mouse Model of Chagas Disease. Where Do the Cells Go?

Jasmin, Linda A. Jelicks, Wade R. Koba, Herbert B. Tanowitz, Rosalia Mendez-Otero, Antonio C. Campos de Carvalho, David C. Spray

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi), is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs) has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease. Methods and Results: We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET). Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS). Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model. Conclusions: We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

Original languageEnglish (US)
Article numbere1971
JournalPLoS Neglected Tropical Diseases
Volume6
Issue number12
DOIs
StatePublished - Dec 2012

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Chagas Disease
Cell- and Tissue-Based Therapy
Bone Marrow Cells
Trypanosoma cruzi
Nanoparticles
Cell Tracking
Parasitic Diseases
Latin America
Acute Disease
Cardiomyopathies
Positron-Emission Tomography
Brazil
Tail
Dilatation
Veins
Heart Diseases
Myocardium
Chronic Disease
Cell Death
Stem Cells

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Mesenchymal Bone Marrow Cell Therapy in a Mouse Model of Chagas Disease. Where Do the Cells Go? / Jasmin; Jelicks, Linda A.; Koba, Wade R.; Tanowitz, Herbert B.; Mendez-Otero, Rosalia; Campos de Carvalho, Antonio C.; Spray, David C.

In: PLoS Neglected Tropical Diseases, Vol. 6, No. 12, e1971, 12.2012.

Research output: Contribution to journalArticle

Jasmin ; Jelicks, Linda A. ; Koba, Wade R. ; Tanowitz, Herbert B. ; Mendez-Otero, Rosalia ; Campos de Carvalho, Antonio C. ; Spray, David C. / Mesenchymal Bone Marrow Cell Therapy in a Mouse Model of Chagas Disease. Where Do the Cells Go?. In: PLoS Neglected Tropical Diseases. 2012 ; Vol. 6, No. 12.
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