在哺乳動物器官中,,肝臟是獨特的,,因為在遭到嚴重性組織損傷或者甚至是手術(shù)部分摘取后,,它能夠再生,。
來自美國南加州大學洛杉磯分校的Laurie DeLeve和她的同事們想要更好地理解哪些細胞特異性地促進肝臟再生,。
人們通常認為一類特殊的細胞,,即肝竇內(nèi)皮細胞(liver sinusoidal endothelial cell),促進肝組織再生,。然而,,DeLeve領(lǐng)導的研究小組猜測能夠分化為成熟細胞類型的干細胞和祖細胞可能通過產(chǎn)生肝細胞生長因子來負責促進肝臟再生。
利用大鼠模式系統(tǒng),,他們首先確定在肝臟和骨髓中存在產(chǎn)生肝竇內(nèi)皮細胞的干細胞和祖細胞,。他們接著研究它們當中哪些細胞群體是肝臟再生所必需的。DeLeve和同事們發(fā)現(xiàn)在沒有損傷時,,骨髓來源的干細胞和祖細胞不是肝細胞增殖所必需的,。
然而,在手術(shù)摘除大鼠部分肝臟之后,,灌注骨髓來源的祖細胞是肝臟再生所必需的,。這些結(jié)果有望加強人們對肝組織遭受損傷后如何再生的理解,而且也可能有助于理解骨髓組織受到抑制的病人產(chǎn)生的肝臟并發(fā)癥,。(生物谷:towersimper編譯)
doi:10.1172/JCI58789
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PMID:
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.