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首页> 外文期刊>Journal of Cellular Physiology >Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells.
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Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells.

机译：增强的增殖和分化的老鼠肝细胞与骨髓基质培养的细胞。

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摘要

Liver transplantation is the only clinically effective method of treating acute liver failure. However, wider application of this therapeutic modality is restricted primarily by shortage of donor organs. In the search for alternative methods of liver replacement therapy, investigators have focused on transplantation of normal allogeneic hepatocytes and on the development of liver support systems utilizing isolated hepatocytes. Since all human livers suitable for cell harvest are being used for transplantation, hepatocyte therapy using human tissue would require growing of cells in vitro. Unfortunately, although hepatocytes have tremendous capacity to proliferate in vivo, their ability to grow in culture is severely limited. Stromal cells from bone marrow and other blood-forming organs have been found to support hematopoiesis. In this paper, we show that bone marrow-derived stromal cells (BMSCs) enhance proliferation and support differentiation of rat hepatocytes in culture. Further, we demonstrate that in hepatocyte/BMSC co-cultures, clonal expansion of small hepatocytes (SH) is increased. Using semipermeable membrane cultures, we established that direct cell-cell contact is necessary for stimulation of cell proliferation. We also show that BMSCs which are in direct contact with hepatocytes and SH colonies express Jagged1. This suggests a potential role for Notch signaling in the observed effects. Finally, we present evidence that the expression and activity of liver specific transcription factors, CCAAT/enhancer binding proteins and liver specific key enzymes such as tryptophan 2,3-dioxygenase, are improved in hepatocyte/BMSC co-cultures. In conclusion, results of this study indicate that BMSCs could facilitate proliferation and differentiation of primary rat hepatocytes and their progenitors (SH) in vitro. Copyright 2001 Wiley-Liss, Inc.
机译：肝移植是唯一临床治疗急性肝衰竭的有效方法。然而,这个治疗的广泛应用形态主要由短缺的限制捐献器官。方法肝替代疗法,调查人员关注的移植同种异体肝细胞和正常肝脏支持系统利用的发展孤立的肝细胞。适合用于细胞收获使用人类移植,肝细胞疗法组织需要的细胞体外生长。不幸的是,尽管肝细胞巨大的体内增殖的能力,他们的生长在文化能力是极其有限的。从骨髓基质细胞和其他发现了支持造血器官造血作用。骨髓来源基质细胞(bmsc)增强鼠干细胞的增殖和支持肝细胞在文化。在肝细胞/ BMSC共培养,克隆扩张的小肝细胞(SH)增加。利用半透膜的文化,我们建立直接联系信息刺激细胞增殖所必需的。我们还表明,bmsc直接与肝细胞和SH殖民地表达Jagged1。信号的观察效果。目前的证据表明,表达和活动肝特定的转录因子,CCAAT /增强子结合蛋白和肝具体的等关键酶色氨酸2 3-dioxygenase在肝细胞/ BMSC改进共培养。表明bmsc可以促进增殖和分化的主要鼠肝细胞和他们的祖细胞(SH)体外。版权2001 Wiley-Liss公司。

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