Reconstruction of the liver useing autologous bone marrow

背景/目的：骨髓细胞具有高度可塑性，可分化为多种细胞类型，包括肝细胞。为了探讨这些过程的机制，我们使用了一个小鼠模型，重点研究了骨髓对肝切除的初始反应。方法：为了评估骨髓细胞的肝分化，我们检测了肝部分切除小鼠肝细胞相关基因的表达，并用2-乙酰氨基荧预处理1周。结果：肝切除诱导了一些与早期肝分化相关的基因在骨髓中的表达。给予AAF后，这些基因的表达增强，但未检测到成熟肝细胞的特异性基因。我们对表达肝细胞分化基因的骨髓细胞群进行了表征。在LIN-、CD34、c-kit、SCA-1、CD49f或CD45细胞中均可诱导甲胎蛋白基因的表达。利用寡核苷酸芯片鉴定AAF治疗和肝切除术后肝脏中上调的基因。这些基因包括与急性期反应相关的基因。地塞米松抑制AAF/PHX小鼠骨髓中早期肝分化基因的表达。结论：肝切除后，尤其是残肝再生受到抑制时，骨髓中可诱导出早期肝分化基因。AAF/PHX肝脏产生的循环信号可能激活了这种分化。

Background/Aims: Bone marrow cells are highly plastic and differentiate into various cell types, including hepatocytes. To explore the mechanisms underlying these processes, we focused on the initial responses of bone marrow to hepatectomy, using a mouse model.Methods: To evaluate hepatic differentiation in bone marrow cells we measured hepatocyte-related gene expression in mice undergoing partial hepatectomy with or without pretreatment for 1 week with 2-acetyl aminofluorene (AAF).Results: Hepatectomy induced several genes related to early hepatic differentiation in bone marrow. Expression of these genes was enhanced by the administration of AAF, whereas genes specific for mature hepatocytes were not detected. We characterised the bone marrow cell population expressing hepatocyte differentiation genes. a-fetoprotein mRNA was induced in Lin-and either CD34+, c-kit+, Sca-1+, CD49f+ or CD45+ cells. The genes upregulated in the liver after AAF treatment and hepatectomy were identified using oligonucleotide microarrays. These included genes associated with the acute phase response. Dexamethasone inhibited the expression of early hepatic differentiation genes in the bone marrow of AAF/PHx mice.Conclusions: Early hepatic differentiation genes were induced in bone marrow in response to hepatectomy, especially when regeneration of the remnant liver was suppressed. Circulating signals generated in the AAF/PHx liver might activate this differentiation.