Intravenous injection of prominin-1-expressing progenitor cells reduced severity scores and preserved fractional shortening in mice with experimental autoimmune myocarditis compared to control.
Does intravenous injection of prominin-1-expressing progenitor cells reduce severity of experimental autoimmune myocarditis in mice?
Prominin-1-expressing bone marrow-derived progenitor cells protect against experimental autoimmune myocarditis and preserve cardiac function in a mouse model.
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.
Kania et al. (Fri,) conducted a other in Experimental autoimmune myocarditis. Prominin-1-expressing progenitor cells (PPC) vs. Phosphate-buffered saline (PBS) or crude bone marrow was evaluated on Severity scores and echocardiographic parameters (fractional shortening and velocity of circumferential shortening). Intravenous injection of prominin-1-expressing progenitor cells reduced severity scores and preserved fractional shortening in mice with experimental autoimmune myocarditis compared to control.