Myelomonocytic cells are sufficient for therapeutic cell fusion in liver
Myelomonocytic cells are sufficient for therapeutic cell fusion in liver
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DOI：
10.1038/nm1062
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发表时间：
2004-07-01
期刊：
影响因子：
82.9
通讯作者：
Grompe, M
中科院分区：
文献类型：
--
作者：
Willenbring, H;Bailey, AS;Grompe, M
用骨髓来源的肝细胞（BMH）进行肝脏重建可以治愈遗传性肝病富马酰乙酰乙酸水解酶（Fah）缺乏症（1）。BMH来自供体骨髓源性细胞和宿主肝细胞之间的融合（2）。为了将这种体内细胞融合有效地用于治疗，需要了解与肝细胞融合的造血细胞的性质。在这里，我们表明，移植到Fah（-/-）小鼠的造血干细胞（HSC）从淋巴细胞缺陷的Rag 1（-/-）小鼠，谱系定型粒细胞-巨噬细胞祖细胞（GMP）或骨髓来源的巨噬细胞（BMHS）的结果在强大的生产BMHS。这些结果提供了直接的证据，即定向粒单核细胞如巨噬细胞可以通过体内融合产生功能性上皮细胞。由于这一过程不需要稳定的骨髓移植或HSC，因此巨噬细胞或其高度增殖的祖细胞为旨在器官再生的靶向和耐受性良好的细胞治疗提供了潜力。
Liver repopulation with bone marrow-derived hepatocytes (BMHs) can cure the genetic liver disease fumarylacetoacetate hydrolase (Fah) deficiency(1). BMHs emerge from fusion between donor bone marrow-derived cells and host hepatocytes(2). To use such in vivo cell fusion efficiently for therapy requires knowing the nature of the hematopoietic cells that fuse with hepatocytes. Here we show that the transplantation into Fah(-/-) mice of hematopoietic stem cells (HSCs) from lymphocyte-deficient Rag1(-/-) mice, lineage-committed granulocyte-macrophage progenitors (GMPs) or bone marrow-derived macrophages (BMMs) results in the robust production of BMHs. These results provide direct evidence that committed myelomonocytic cells such as macrophages can produce functional epithelial cells by in vivo fusion. Because stable bone marrow engraftment or HSCs are not required for this process, macrophages or their highly proliferative progenitors provide potential for targeted and well-tolerated cell therapy aimed at organ regeneration.