Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-11962
Kania, G; Blyszczuk, P; Valaperti, A; Dieterle, T; Leimenstoll, B; Dirnhofer, S; Zulewski, H; Eriksson, U (2008). Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis. Cardiovascular Research, 80(2):236-245.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology|
|DDC:||610 Medicine & health|
|Date:||01 November 2008|
|Deposited On:||03 Feb 2009 17:34|
|Last Modified:||23 Nov 2012 14:19|
|Publisher:||Oxford University Press|
|Additional Information:||This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The definitive publisher-authenticated version Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis is available online http://cardiovascres.oxfordjournals.org/cgi/content/abstract/80/2/236|
|Free access at:||PubMed ID. An embargo period may apply.|
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