Kania, G. and Blyszczuk, P. and Valaperti, A. and Dieterle, T. and Leimenstoll, B. and Dirnhofer, S. and Zulewski, H. and Eriksson, U.. (2008) Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis. Cardiovascular research, Vol. 80, H. 2. pp. 236-245.
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Official URL: http://edoc.unibas.ch/dok/A6006049
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Abstract
AIMS: Experimental autoimmune myocarditis (EAM) is a CD4(+) T cell-mediated mouse model of inflammatory heart disease. Tissue-resident bone marrow-derived cells adopt different cellular phenotypes depending on the local milieu. We expanded a specific population of bone marrow-derived prominin-1-expressing progenitor cells (PPC) from healthy heart tissue, analysed their plasticity, and evaluated their capacity to protect mice from EAM and heart failure. METHODS AND RESULTS: PPC were expanded from healthy mouse hearts. Analysis of CD45.1/CD45.2 chimera mice confirmed bone marrow origin of PPC. Depending on in vitro culture conditions, PPC differentiated into macrophages, dendritic cells, or cardiomyocyte-like cells. In vivo, PPC acquired a cardiac phenotype after direct injection into healthy hearts. Intravenous injection of PPC into myosin alpha heavy chain/complete Freund's adjuvant (MyHC-alpha/CFA)-immunized BALB/c mice resulted in heart-specific homing and differentiation into the macrophage phenotype. Histology revealed reduced severity scores for PPC-treated mice compared with control animals [treated with phosphate-buffered saline (PBS) or crude bone marrow at day 21 after MyHC-alpha/CFA immunization]. Echocardiography showed preserved fractional shortening and velocity of circumferential shortening in PPC but not PBS-treated MyHC-alpha/CFA-immunized mice. In vitro and in vivo data suggested that interferon-gamma signalling on PPC was critical for nitric oxide-mediated suppression of heart-specific CD4(+) T cells. Accordingly, PPC from interferon-gamma receptor-deficient mice failed to protect MyHC-alpha/CFA-immunized mice from EAM. CONCLUSION: Prominin-1-expressing, heart-resident, bone marrow-derived cells combine high plasticity, T cell-suppressing capacity, and anti-inflammatory in vivo effects.
Faculties and Departments: | 03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Stationäre innere Medizin (Schifferli) 03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Ehemalige Einheiten Medizinische Fächer (Klinik) > Stationäre innere Medizin (Schifferli) 03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Kardiologie 03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Kardiologie 03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie 03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Endokrinologie / Diabetologie 03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer) 03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Histopathologie (Dirnhofer) |
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UniBasel Contributors: | Dirnhofer, Stephan and Eriksson, Urs and Zulewski, Henryk and Dieterle, Thomas |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | Oxford University Press |
ISSN: | 0008-6363 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Related URLs: | |
Identification Number: |
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Last Modified: | 08 Nov 2012 16:23 |
Deposited On: | 08 Nov 2012 16:21 |
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