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Therapeutic applications of bone marrow-derived stem cells in liver transplantation for end-stage liver diseases

机译:骨髓干细胞在肝移植治疗晚期肝病中的治疗应用

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Today, liver transplantation (LT) is the only established treatment for end-stage liver diseases. The development of LT, including OLT, cadaveric LT, split LT, living donor LT (LDLT), brings hopes to patients with these diseases. However, increasing donor shortage, rejection and life-long immunosuppression with its side effects are the major limitations of this therapy strategy. Bone marrow-derived stem cells (BMDSCs) are capable of differentiating into hepatocyte-like cells and contribute to liver injury repair. The microenvironment of liver injury caused by rejection, ischemia/reperfusion, loss of liver mass, recurrence of HCV and "small-for-size syndrome" after LT can attract a variety of bone marrow-derived stem cell population to the peripheral circulation and then migration to the injury liver to promote the hepatic function restoration. Additionally, BMDSCs can also take part in the functional regeneration of living donor liver after LDLT. This participation in liver regeneration may be associated to the interaction between SDF-1and its receptor CXCR4, involving HGF, IL-8, MMP9, and VEGF/VEGFR-2. BMDSC with its bio-characteristics could maintain the allograft tolerance from different angles and in different ways. In conclusion, BMDSCs transplantation, as a new assistant therapeutic method for LT, will expand the space of LT, and provide more survival opportunities for the patients suffering liver diseases in the future.
机译:如今,肝移植(LT)是终末期肝病的唯一公认治疗方法。包括OLT,尸体LT,分裂LT,活体供体LT(LDLT)在内的LT的发展为患有这些疾病的患者带来了希望。然而,供体短缺,排斥反应和终生免疫抑制及其副作用的增加是该治疗策略的主要局限性。骨髓干细胞(BMDSC)能够分化为类肝细胞,并有助于修复肝损伤。排斥反应,局部缺血/再灌注,肝量减少,HCV复发和LT后的“小尺寸综合征”所引起的肝损伤的微环境可以吸引多种源自骨髓的干细胞群体进入外周循环,然后迁移至损伤肝脏以促进肝功能恢复。此外,BMDSCs还可以参与LDLT后活体供体肝脏的功能再生。肝脏再生的这种参与可能与SDF-1及其受体CXCR4之间的相互作用有关,涉及HGF,IL-8,MMP9和VEGF / VEGFR-2。 BMDSC具有其生物特征,可以从不同角度和不同方式维持同种异体移植耐受性。总之,BMDSCs移植作为LT的一种新的辅助治疗方法,将扩大LT的空间,并为将来患肝病的患者提供更多的生存机会。

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