Stem cell mobilization is life saving in an animal model of acute liver failure.
Stem cell mobilization is life saving in an animal model of acute liver failure.
复制标题
干细胞动员是在急性肝衰竭的动物模型中挽救生命。
DOI：
10.1097/sla.0b013e3181f4e479
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发表时间：
2010-10
影响因子：
9
通讯作者：
Cameron AM
中科院分区：
文献类型：
--
作者：
Mark AL;Sun Z;Warren DS;Lonze BE;Knabel MK;Melville Williams GM;Locke JE;Montgomery RA;Cameron AM
目的：急性肝功能衰竭（ALF）患者目前除肝移植外无其他治疗方法。本研究的目的是确定内源性造血干细胞（HSC）的药理动员是否可以帮助肝修复和提高生存率的动物模型ALF.Methods：啮齿动物进行了处理与一个单一的近致死腹腔注射四氯化碳（CCl 4）。12小时后，动物随机接受普乐沙福和粒细胞集落刺激因子（G-CSF）（已知可动员骨髓源性干细胞的药物）或生理盐水溶媒注射。观察小鼠的存活情况，并通过血清转氨酶测定和组织学分析进行一系列评估肝损伤。结果：在我们的ALF模型中，注射CCl 4后7天存活率为25%。在CCl 4后给予plerixafor和G-CSF导致87%的存活率（n= 8，P< 0.05）。在系列组织病理学分析中，与对照组动物相比，普乐沙福和G-CSF治疗组动物的肝损伤较轻。外周血的评价表明，循环中的肝星状细胞在plerixafor和G-CSF的反应增加，和免疫染色表明肝星状细胞浸润到肝实质后干细胞mobilization.Conclusions：我们的研究结果表明，一个可能的新的治疗策略与ALF患者，一组人要么肝移植或死亡是经常的结果。动员HSC的药物可能导致受损肝脏的细胞浸润，这些细胞可能参与或加速肝脏再生。这种疗法有可能避免一些ALF患者的肝移植，并可能对各种各样的肝损伤内科和外科患者有益。
Objective:No therapy except liver transplantation currently exists for patients with acute liver failure (ALF). The aim of this study was to determine whether pharmacologic mobilization of endogenous hematopoietic stem cells (HSCs) can aid in liver repair and improve survival in an animal model of ALF.Methods:Rodents were treated with a single near-lethal intraperitoneal injection of carbon tetrachloride (CCl 4). After 12 hours, animals were randomized to receive plerixafor and granulocyte colony-stimulating factor (G-CSF), agents known to mobilize marrow-derived stem cells, or saline vehicle injection. Mice were observed for survival, and serial assessment of liver injury by serum transaminase measurements, and histologic analysis was performed.Results:In our ALF model, 7-day survival after injection of CCl 4 was 25%. Administration of plerixafor and G-CSF following CCl 4 resulted in 87% survival (n= 8, P< 0.05). On serial histopathologic analysis, animals treated with plerixafor and G-CSF demonstrated less hepatic injury compared with control animals. Evaluation of peripheral blood demonstrated an increase in circulating HSCs in response to plerixafor and G-CSF, and immunostaining suggested the infiltration of HSCs into the hepatic parenchyma after stem cell mobilization.Conclusions:Our results suggest a possible new treatment strategy for patients with ALF, a group for whom either liver transplantation or death is frequently the outcome. Pharmacologic agents that mobilize HSCs may lead to an infiltration of the injured liver with cells that may participate in or expedite liver regeneration. This therapy has the potential to avert liver transplantation in some patients with ALF and may be of benefit in a wide variety of medical and surgical patients with liver injury.