Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation
Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation
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DOI：
10.1002/hep.510310135
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发表时间：
2000-01-01
期刊：
影响因子：
13.5
通讯作者：
Krause, DS
中科院分区：
文献类型：
--
作者：
Theise, ND;Badve, S;Krause, DS
继骨髓细胞再生骨骼肌的报道之后，我们研究了肝细胞是否也可以在体内从骨髓细胞中获得。一组受致死性照射的B6D2F1雌性小鼠接受年龄匹配的雄性供体的全骨髓移植，并在移植后第1、3、5、7天和第2、4、6个月处死（每个时间点n = 3）。此外，在相同的方案下，在移植后8个月，2只同一品系的雌性档案小鼠被处死，这些雌性小鼠先前接受了200个雄性荧光激活细胞分选器（FACS）分选的CD34(+)lin（-）细胞。对肝组织进行y染色体荧光原位杂交（FISH）。移植后7天，在1只动物和移植后2个月或更长时间的所有动物中，均鉴定出y阳性肝细胞，占总肝细胞的2.2%。同时对y染色体和白蛋白信使RNA （mRNA）的FISH检测证实雄性来源的细胞是成熟的肝细胞。这些动物在骨髓移植时接受了致死剂量的辐射，但这没有引起明显的、组织学上可证明的急性肝损伤，包括炎症、坏死、卵形细胞增殖或疤痕。我们得出结论，在没有严重急性损伤的情况下，肝细胞可以从照射后的骨髓细胞中衍生出来。此外，CD34(+)lin（-）骨髓细胞的小亚群能够进行肝移植。
Following a report of skeletal muscle regeneration from bone marrow cells, we investigated whether hepatocytes could also derive in vivo from bone marrow cells. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 posttransplantation (n = 3 for each time point). Additionally, 2 archival female mice of the same strain who had previously been recipients of 200 male fluorescence-activated cell sorter (FACS)-sorted CD34(+)lin(-) cells were sacrificed 8 months posttransplantation under the same protocol. Fluorescence in situ hybridization (FISH) for the Y-chromosome was performed on liver tissue. Y-positive hepatocytes, up to 2.2% of total hepatocytes, were identified in 1 animal at 7 days posttransplantation and in all animals sacrificed 2 months or longer posttransplantation. Simultaneous FISH for the Y-chromosome and albumin messenger RNA (mRNA) confirmed male-derived cells were mature hepatocytes. These animals had received lethal doses of irradiation at the time of bone marrow transplantation, but this induced no overt, histologically demonstrable, acute hepatic injury, including inflammation, necrosis, oval cell proliferation, or scarring. We conclude that hepatocytes can derive from bone marrow cells after irradiation in the absence of severe acute injury. Also, the small subpopulation of CD34(+)lin(-) bone marrow cells is capable of such hepatic engraftment.