Oh Keunhee, Shon Suh Youn, Seo Myung Won, Lee Hak Mo, Oh Ju-Eun, Choi Eun Young, Lee Dong-Sup, Park Kyong Soo
Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Exp Mol Med. 2015 Oct 2;47(10):e187. doi: 10.1038/emm.2015.64.
The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1(+) subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.
骨髓细胞直接分化为肝细胞仍存在争议。针对这一现象，已经提出了几种机制，包括转分化和细胞融合，尽管该过程及其潜在机制尚未有直接可视化报道。在本研究中，我们建立了一种高效的体外培养方法，用于从小鼠谱系阴性骨髓细胞分化出功能性肝细胞。在两个独立的肝损伤模型中，这些细胞减轻了肝损伤并整合到肝实质中。我们用于内胚层前体细胞存活和扩增的简单高效体外方案，使我们能够将这些细胞鉴定为存在于谱系阴性骨髓细胞的Sca1(+)亚群中。内胚层前体细胞遵循一个连续的发育途径，包括内胚层细胞和肝细胞前体细胞，这表明谱系阴性骨髓细胞包含比以前认为的更多样化的多能干细胞。人类骨髓中存在等效的内胚层前体细胞群将有助于将这些细胞开发成一种有效的慢性肝病治疗方式。
