Rescue of lethal hepatic failure by hepatized lymph nodes in mice.
Rescue of lethal hepatic failure by hepatized lymph nodes in mice.
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DOI：
10.1053/j.gastro.2010.11.006
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发表时间：
2011-02
期刊：
影响因子：
29.4
通讯作者：
Lagasse E
中科院分区：
文献类型：
--
作者：
Hoppo T;Komori J;Manohar R;Stolz DB;Lagasse E
肝细胞移植是一种潜在的治疗肝病的方法。然而，大多数慢性肝损伤患者患有肝硬化和纤维化，这限制了基于细胞的肝脏治疗的潜力。异位肝作为肝功能的额外部位的发展代表了终末期肝病患者的新方法。我们研究了肝衰竭小鼠淋巴结中肝组织的发育和功能。从8 - 12周龄小鼠中分离肝细胞，并通过腹膜内注射移植到8- 12周龄Fah-/-小鼠（人肝病酪氨酸血症I型模型）中。监测存活率，并确定移植肝细胞的位置和功能。Fah-/-小鼠的淋巴结被移植的肝细胞定殖;在淋巴系统的CD 45+淋巴样细胞附近检测到Fah+肝细胞。移植后10周，这些小鼠的血清转氨酶、胆红素和氨基酸水平有实质性改善。供体肝细胞在淋巴结中的稳态扩增使小鼠免于致死性肝功能衰竭。淋巴结中的功能性异位肝组织可使小鼠免于致死性肝病;因此淋巴结可用作肝细胞移植的部位。
Hepatocyte transplantation is a potential therapeutic approach for liver disease. However, most patients with chronic hepatic damage have cirrhosis and fibrosis, which limit the potential for cell-based therapy of the liver. The development of an ectopic liver as an additional site of hepatic function represents a new approach for patients with an end-stage liver disease. We investigated the development and function of liver tissue in lymph nodes in mice with liver failure. Hepatocytes were isolated from 8 to 12-week-old mice and transplanted by intraperitoneal injection into 8- to 12-week-old Fah-/- mice, a model of the human liver disease tyrosinemia type I. Survival was monitored and the locations and functions of the engrafted liver cells were determined. Lymph nodes of Fah-/- mice were colonized by transplanted hepatocytes; Fah+ hepatocytes were detected adjacent to the CD45+ lymphoid cells of the lymphatic system. Ten weeks after transplantation, these mice had substantial improvements in serum levels of transaminases, bilirubin, and amino acids. Homeostatic expansion of donor hepatocytes in lymph nodes rescued the mice from lethal hepatic failure. Functional ectopic liver tissue in lymph nodes rescues mice from lethal hepatic disease; lymph nodes might therefore be used as sites for hepatocyte transplantation.
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