Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners.
Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners.
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造血粒单核细胞是肝细胞融合伙伴的主要来源。
DOI：
10.1172/jci21301
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Goodell,MargaretA
中科院分区：
文献类型：
--
作者：
Camargo,FernandoD;Finegold,Milton;Goodell,MargaretA
最近的一些报道表明，骨髓细胞移植可以产生有功能的肝细胞。骨髓来源的细胞与宿主肝细胞之间的细胞融合被证明是这种现象的机制。然而，介导细胞融合的骨髓细胞的确切身份仍然不确定。在这里，我们证明了单个造血干细胞(HSC)的造血子代足以产生功能性的肝脏再生。此外，淋巴细胞缺陷的骨髓细胞移植和体内髓系的命运图谱显示，HSC来源的肝细胞主要来自成熟的骨髓单核细胞。此外，使用基于Cre/LOX的策略，我们直接证明了髓系细胞自发地与宿主肝细胞融合。我们的发现增加了分化的髓系细胞可能对未来体内细胞融合的治疗应用有用的可能性。
Several recent reports have demonstrated that transplantation of bone marrow cells can result in the generation of functional hepatocytes. Cellular fusion between bone marrow–derived cells and host hepatocytes has been shown to be the mechanism of this phenomenon. However, the exact identity of the bone marrow cells that mediate cellular fusion has remained undetermined. Here we demonstrate that the hematopoietic progeny of a single hematopoietic stem cell (HSC) is sufficient to produce functional hepatic repopulation. Furthermore, transplantation of lymphocyte-deficient bone marrow cells and in vivo fate mapping of the myeloid lineage revealed that HSC-derived hepatocytes are primarily derived from mature myelomonocytic cells. In addition, using a Cre/lox–based strategy, we directly demonstrate that myeloid cells spontaneously fuse with host hepatocytes. Our findings raise the possibility that differentiated myeloid cells may be useful for future therapeutic applications of in vivo cellular fusion.