Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats
Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats
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DOI：
10.1172/jci58789
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发表时间：
2012-04-01
影响因子：
15.9
通讯作者：
DeLeve, Laurie D.
中科院分区：
文献类型：
--
作者：
Wang, Lin;Wang, Xiangdong;DeLeve, Laurie D.
肝脏的再生能力对于损伤后和慢性疾病期间保护肝功能至关重要。肝窦内皮细胞（LSECs）中肝细胞生长因子（HGF）的增加被认为可以推动肝脏再生。然而，与内皮祖细胞相比，成熟的LSECs表达少量HGF。因此，我们试图在大鼠身上建立肝损伤是否会导致BM LSEC祖细胞植入肝脏并增加HGF水平，并检查常驻和BM LSEC祖细胞的相对贡献。肝脏中发现LSEC标记保留细胞和祖细胞，BM中发现LSEC祖细胞。BM LSEC祖细胞不能促进肝脏中正常的LSEC转化。然而，在部分肝切除术后，BM LSEC祖细胞增殖和向循环的动员增加了一倍。在肝脏中，四分之一的LSECs是BM来源的，BM LSEC祖细胞分化为开孔LSECs。当受辐射的大鼠进行部分肝切除术时，肝脏再生受到损害，但输注LSEC祖细胞可挽救缺陷。进一步的分析显示，在部分肝切除术后，BM LSEC祖细胞比原位LSEC祖细胞表达了更多的HGF，并具有更强的增殖能力。与BM LSEC祖细胞相比，原位LSEC祖细胞在部分肝切除术后的恢复中可能发挥的作用较小，但是，当损伤后输注时，这些祖细胞在2个月的时间内移植并显著扩大。综上所述，肝脏和骨髓中均存在LSEC祖细胞，骨髓中LSEC祖细胞的募集是正常肝脏再生所必需的。
The ability of the liver to regenerate is crucial to protect liver function after injury and during chronic disease. Increases in hepatocyte growth factor (HGF) in liver sinusoidal endothelial cells (LSECs) are thought to drive liver regeneration. However, in contrast to endothelial progenitor cells, mature LSECs express little HGF. Therefore, we sought to establish in rats whether liver injury causes BM LSEC progenitor cells to engraft in the liver and provide increased levels of HGF and to examine the relative contribution of resident and BM LSEC progenitors. LSEC label-retaining cells and progenitors were identified in liver and LSEC progenitors in BM. BM LSEC progenitors did not contribute to normal LSEC turnover in the liver. However, after partial hepatectomy, BM LSEC progenitor proliferation and mobilization to the circulation doubled. In the liver, one-quarter of the LSECs were BM derived, and BM LSEC progenitors differentiated into fenestrated LSECs. When irradiated rats underwent partial hepatectomy, liver regeneration was compromised, but infusion of LSEC progenitors rescued the defect. Further analysis revealed that BM LSEC progenitors expressed substantially more HGF and were more proliferative than resident LSEC progenitors after partial hepatectomy. Resident LSEC progenitors within their niche may play a smaller role in recovery from partial hepatectomy than BM LSEC progenitors, but, when infused after injury, these progenitors engrafted and expanded markedly over a 2-month period. In conclusion, LSEC progenitor cells are present in liver and BM, and recruitment of BM LSEC progenitors is necessary for normal liver regeneration.