Theise N D, Badve S, Saxena R, Henegariu O, Sell S, Crawford J M, Krause D S
Department of Pathology, New York University, School of Medicine, New York, NY 10016, USA.
Hepatology. 2000 Jan;31(1):235-40. doi: 10.1002/hep.510310135.
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.
在有报道称骨髓细胞可实现骨骼肌再生之后，我们研究了肝细胞是否也能在体内源自骨髓细胞。一组接受致死剂量照射的B6D2F1雌性小鼠接受了来自年龄匹配雄性供体的全骨髓移植，并在移植后第1、3、5和7天以及第2、4和6个月处死（每个时间点n = 3）。此外，按照相同方案，对2只先前接受过200个经荧光激活细胞分选仪（FACS）分选的雄性CD34(+)lin(-)细胞移植的同品系存档雌性小鼠在移植后8个月进行处死。对肝组织进行Y染色体的荧光原位杂交（FISH）。在移植后7天的1只动物以及移植后2个月或更长时间处死的所有动物中，均鉴定出Y阳性肝细胞，其比例高达肝细胞总数的2.2%。同时对Y染色体和白蛋白信使核糖核酸（mRNA）进行FISH证实，雄性来源的细胞为成熟肝细胞。这些动物在骨髓移植时接受了致死剂量的照射，但未引发明显的、组织学上可证实的急性肝损伤，包括炎症、坏死、卵圆细胞增殖或瘢痕形成。我们得出结论，在无严重急性损伤的情况下，照射后肝细胞可源自骨髓细胞。此外，CD34(+)lin(-)骨髓细胞的小亚群能够实现这种肝脏植入。
