CD39 Modulates Hematopoietic Stem Cell Recruitment and Promotes Liver Regeneration in Mice and Humans After Partial Hepatectomy
CD39 Modulates Hematopoietic Stem Cell Recruitment and Promotes Liver Regeneration in Mice and Humans After Partial Hepatectomy
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CD39 调节造血干细胞募集并促进部分肝切除术后小鼠和人类的肝脏再生
DOI：
10.1097/sla.0b013e31826c3ec2
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发表时间：
2013
影响因子：
9
通讯作者：
S. C. Robson
中科院分区：
文献类型：
--
作者：
M. Schmelzle;C. Duhme;W. Junger;S.D. Salhanick;Y. Chen;V. Toxavidis;E. Csizmadia;L. Han;S. Bian;G. Fürst;M. Nowak;S. J. Karp;W. T. Knoefel;J. Schulte Esch;S. C. Robson
目的：研究肝切除术后造血干细胞（hematopoietic stem cell，HSC）动员的分子机制及其对肝再生的影响。CD 39家族的外核苷酸酶表达的骨髓来源的细胞，嘌呤能机制也可能影响动员和功能的HSC后liver injury.Methods：部分肝切除术进行C57 BL/6野生型，Cd 39外核苷酸酶无效小鼠和嵌合小鼠移植后的野生型或Cd 39无效骨髓。骨髓来源的HSC通过荧光激活细胞分选纯化，并在肝切除术后施用。进行了体外趋化性研究，以检查嘌呤能受体激动剂和拮抗剂的作用。动员的人HSC和CD 39的表达进行了检查，并连接到切除和肝脏tests.Results的程度：部分肝切除术后，优先动员的HSC表达Cd 39的亚群。在体外，HSC的趋化反应通过CD 39依赖的三磷酸腺苷水解和经由A2 A受体的腺苷信号传导而增加。动员的Cd 39高HSC促进肝再生，可能限制白细胞介素1β信号传导。在临床研究中，动员的人HSC也以高水平表达CD 39。动员的HSC直接与恢复肝脏体积和功能后，部分hepatectomy.Conclusions：我们证明CD 39是一种新的HSC标记，定义了一个功能不同的干细胞亚群在小鼠和人类。HSC在肝切除后被动员，限制炎症，并以CD 39依赖性方式促进再生。这些观察结果对监测具有影响，并指示未来的治疗途径。
Objective:To study molecular mechanisms involved in hematopoietic stem cell (HSC) mobilization after liver resection and determine impacts on liver regeneration.Background:Extracellular nucleotide-mediated cell signaling has been shown to boost liver regeneration. Ectonucleotidases of the CD39 family are expressed by bone marrow–derived cells, and purinergic mechanisms might also impact mobilization and functions of HSC after liver injury.Methods:Partial hepatectomy was performed in C57BL/6 wild-type, Cd39 ectonucleotidase-null mice and in chimeric mice after transplantation of wild-type or Cd39-null bone marrow. Bone marrow–derived HSCs were purified by fluorescence-activated cell sorting and administered after hepatectomy. Chemotactic studies were performed to examine effects of purinergic receptor agonists and antagonists in vitro. Mobilization of human HSCs and expression of CD39 were examined and linked to the extent of resection and liver tests.Results:Subsets of HSCs expressing Cd39 are preferentially mobilized after partial hepatectomy. Chemotactic responses of HSCs are increased by CD39-dependent adenosine triphosphate hydrolysis and adenosine signaling via A2A receptors in vitro. Mobilized Cd39 high HSCs boost liver regeneration, potentially limiting interleukin 1β signaling. In clinical studies, mobilized human HSCs also express CD39 at high levels. Mobilization of HSCs correlates directly with the restoration of liver volume and function after partial hepatectomy.Conclusions:We demonstrate CD39 to be a novel HSC marker that defines a functionally distinct stem cell subset in mice and humans. HSCs are mobilized after liver resection, limit inflammation, and boost regeneration in a CD39-dependent manner. These observations have implications for monitoring and indicate future therapeutic avenues.
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影响因子：
29.4
作者：
Harb R;Xie G;Lutzko C;Guo Y;Wang X;Hill CK;Kanel GC;DeLeve LD
通讯作者：
DeLeve LD
影响因子：
4.4
作者：
Ghannam, Soufiane;Pene, Jerome;Yssel, Hans
通讯作者：
Yssel, Hans
影响因子：
10.8
作者：
Kania, Gabriela;Blyszczuk, Przemyslaw;Eriksson, Urs
通讯作者：
Eriksson, Urs
影响因子：
29.4
作者：
Petrasek J;Dolganiuc A;Csak T;Kurt-Jones EA;Szabo G
通讯作者：
Szabo G
影响因子：
2.4
作者：
Beaudry, Pau;Hida, Yasuhiro;Puder, Mark
通讯作者：
Puder, Mark