Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis
Prominin-1+/CD133+ bone marrow-derived heart-resident cells suppress experimental autoimmune myocarditis
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DOI：
10.1093/cvr/cvn190
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发表时间：
2008-11-01
影响因子：
10.8
通讯作者：
Eriksson, Urs
中科院分区：
文献类型：
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作者：
Kania, Gabriela;Blyszczuk, Przemyslaw;Eriksson, Urs
实验性自身免疫性心肌炎（EAM）是一种CD 4（+）T细胞介导的炎症性心脏病小鼠模型。组织驻留骨髓源性细胞根据局部环境采用不同的细胞表型。我们扩大了一个特定的人口的骨髓来源的repeatin-1表达祖细胞（PPC）从健康的心脏组织，分析其可塑性，并评估其能力，以保护小鼠从EAM和heart failure.Methods和结果PPC从健康的小鼠心脏扩大。对CD45.1/CD45.2嵌合体小鼠的分析证实PPC的骨髓来源。根据体外培养条件，PPC分化为巨噬细胞、树突状细胞或心肌细胞样细胞。在体内，PPC在直接注射到健康心脏后获得心脏表型。将PPC静脉注射到肌球蛋白α重链/完全弗氏佐剂（MyHC-alpha/CFA）免疫的BALB/c小鼠中导致心脏特异性归巢和分化成巨噬细胞表型。组织学显示，与对照动物相比，PPC处理的小鼠的严重程度评分降低[在MyHC-alpha/CFA免疫后第21天用磷酸盐缓冲盐水（PBS）或粗骨髓处理]。超声心动图显示PPC中保留了缩短分数和圆周缩短速度，但PBS处理的MyHC-α/CFA免疫小鼠则没有。体外和体内数据表明，PPC上的干扰素-γ信号对于一氧化氮介导的心脏特异性CD 4（+）T细胞抑制至关重要。因此，PPC从干扰素γ受体缺陷小鼠未能保护MyHC-α/CFA免疫小鼠从EAM.Conclusion Prominin-1表达，心脏驻留，骨髓来源的细胞联合收割机结合高可塑性，T细胞抑制能力，和抗炎作用在体内。
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.