Misawa Ryosuke, Ise Hirohiko, Takahashi Masafumi, Morimoto Hajime, Kobayashi Eiji, Miyagawa Shin-ichi, Ikeda Uichi
Department of Organ Regeneration, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Biochem Biophys Res Commun. 2006 Apr 7;342(2):434-40. doi: 10.1016/j.bbrc.2006.01.169. Epub 2006 Feb 9.
Several recent studies have reported that bone marrow cells (BMCs) have the ability to generate functional hepatocytes. However, the efficiency at which BMC transplantation generates functional hepatocytes is rather low. We assumed that if BMCs accumulated directly in liver, the functional BMC-derived hepatocytes should increase efficiently. We tried to increase the accumulation of BMCs directly in liver through the interaction between hepatic asialoglycoprotein receptor and desialylated BMCs. Desialylated BMCs were produced with treatment of neuraminidase. Desialylated BMCs that expressed green fluorescent protein (GFP) were injected into Long Evans Cinnamon (LEC) rats, a human Wilson's disease model, intravenously. At 3 and 5 months after transplantation, GFP-expressing hepatocyte nodules appeared in the liver of these BMC-transplanted LEC rats. These findings suggest that the functional BMC-derived hepatocytes can be generated by the direct accumulation of BMCs and that this strategy is new BMC therapy for liver regeneration.
最近的几项研究报告称，骨髓细胞（BMCs）具有生成功能性肝细胞的能力。然而，BMC移植产生功能性肝细胞的效率相当低。我们推测，如果BMCs直接在肝脏中积累，那么源自BMC的功能性肝细胞应该会有效增加。我们试图通过肝去唾液酸糖蛋白受体与去唾液酸化的BMCs之间的相互作用，来增加BMCs在肝脏中的直接积累。用神经氨酸酶处理制备出去唾液酸化的BMCs。将表达绿色荧光蛋白（GFP）的去唾液酸化BMCs静脉注射到人类威尔逊病模型——长Evans肉桂色（LEC）大鼠体内。在移植后3个月和5个月时，这些接受BMC移植的LEC大鼠的肝脏中出现了表达GFP的肝细胞结节。这些发现表明，功能性BMC衍生的肝细胞可以通过BMCs的直接积累产生，并且这种策略是用于肝脏再生的新型BMC治疗方法。
