在哺乳动物器官中,肝脏是独特的,因为在遭到严重性组织损伤或者甚至是手术部分摘取后,它能够再生。
来自美国南加州大学洛杉矶分校的Laurie DeLeve和她的同事们想要更好地理解哪些细胞特异性地促进肝脏再生。
人们通常认为一类特殊的细胞,即肝窦内皮细胞(liver sinusoidal endothelial cell),促进肝组织再生。然而,DeLeve领导的研究小组猜测能够分化为成熟细胞类型的干细胞和祖细胞可能通过产生肝细胞生长因子来负责促进肝脏再生。
利用大鼠模式系统,他们首先确定在肝脏和骨髓中存在产生肝窦内皮细胞的干细胞和祖细胞。他们接着研究它们当中哪些细胞群体是肝脏再生所必需的。DeLeve和同事们发现在没有损伤时,骨髓来源的干细胞和祖细胞不是肝细胞增殖所必需的。
然而,在手术摘除大鼠部分肝脏之后,灌注骨髓来源的祖细胞是肝脏再生所必需的。这些结果有望加强人们对肝组织遭受损伤后如何再生的理解,而且也可能有助于理解骨髓组织受到抑制的病人产生的肝脏并发症。(生物谷:towersimper编译)
doi:10.1172/JCI58789
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Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats
Lin Wang, Xiangdong Wang, Guanhua Xie, Lei Wang, Colin K. Hill and Laurie D. DeLeve
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.