Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats.
Pharmacological Mobilization of Endogenous Bone Marrow Stem Cells Promotes Liver Regeneration after Extensive Liver Resection in Rats.
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DOI：
10.1038/s41598-018-21961-2
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发表时间：
2018-02-26
影响因子：
4.6
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Zhai R;Wang Y;Qi L;Williams GM;Gao B;Song G;Burdick JF;Sun Z
残肝的快速再生是预防广泛肝切除术后肝功能衰竭和促进术后恢复的关键。许多研究已经证明了骨髓来源的干细胞参与肝再生和骨髓干细胞治疗的潜在益处。为了避免干细胞的制备，我们在本研究中提出用CXCR 4拮抗剂AMD 3100（A）和低剂量FK 506（F）联合动员内源性骨髓干细胞。在此，我们发现AF联合治疗显著增加外周血中谱系阴性（Lin-）CD 34+和Lin-CD 133+干细胞，并增强了85%部分肝切除大鼠模型中CD 133+细胞向残肝的募集。在残肝中募集CD 133+干细胞与肝卵圆细胞增殖增加相关，并抑制SDF-1、CXCR 4和HGF表达增加。重要的是，AF联合治疗增加了Ki 67阳性肝细胞的数量和残肝中BrdU的掺入，并改善了血清白蛋白水平。我们的研究结果表明，AF联合治疗的内源性骨髓干细胞的药物动员可以增强内源性干细胞动员，以促进广泛肝切除术后的肝再生和改善肝功能。
Rapid regeneration of the remnant liver is critical for preventing liver failure and promoting recovery after extensive liver resection. Numerous studies have demonstrated the involvement of bone marrow-derived stem cells in liver regeneration and the potential benefits of bone marrow stem cell therapy. To avoid the preparation of stem cells, we proposed in this study to mobilize endogenous bone marrow stem cells pharmacologically with a combination of AMD3100 (A), an antagonist of CXCR4 and low-dose FK506 (F). Here we show that AF combination therapy significantly increased lineage negative (Lin-) CD34+ and Lin-CD133+ stem cells in peripheral blood and enhanced recruitment of CD133+ cells into the remnant liver in a rat model of 85% partial hepatectomy. Recruiting CD133+ stem cells in the remnant liver was associated with increased proliferation of hepatic oval cells and paralleled the increased SDF-1, CXCR4 and HGF expression. Importantly, AF combination therapy increased the number of Ki67 positive hepatocytes and BrdU incorporation in the remnant liver and improved serum levels of albumin. Our results demonstrate that pharmacological mobilization of endogenous bone marrow stem cells with AF combination therapy can enhance endogenous stem cell mobilization to promote liver regeneration and improve liver function after extensive hepatectomy.
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影响因子：
6.5
作者：
Lin, Qing;Wesson, Russell N.;Maeda, Hiromichi;Wang, Yongchun;Cui, Zhu;Liu, Jun O.;Cameron, Andrew M.;Gao, Bin;Montgomery, Robert A.;Williams, George M.;Sun, Zhaoli
通讯作者：
Sun, Zhaoli
影响因子：
3.2
作者：
Kuramitsu, Kaori;Fukumoto, Takumi;Ku, Yonson
通讯作者：
Ku, Yonson
影响因子：
25.7
作者：
Fujii, H;Hirose, T;Yamaoka, Y
通讯作者：
Yamaoka, Y
影响因子：
4.3
作者：
Papanikolaou IG;Katselis C;Apostolou K;Feretis T;Lymperi M;Konstadoulakis MM;Papalois AE;Zografos GC
通讯作者：
Zografos GC
DOI：
10.1111/ajt.13706
发表时间：
2016-07
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Hu X;Okabayashi T;Cameron AM;Wang Y;Hisada M;Li J;Raccusen LC;Zheng Q;Montgomery RA;Williams GM;Sun Z
通讯作者：
Sun Z