Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury.
Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury.
复制标题
DOI：
10.1053/j.gastro.2009.05.009
复制
发表时间：
2009-08
期刊：
影响因子：
29.4
通讯作者：
DeLeve LD
中科院分区：
文献类型：
--
作者：
Harb R;Xie G;Lutzko C;Guo Y;Wang X;Hill CK;Kanel GC;DeLeve LD
肝窦内皮细胞（SEC）的损伤引发窦阻塞综合征（SOS），这是最常见的清髓性化学辐射或摄入吡咯里西啶生物碱如野百合碱（Mct）的结果。本研究检查SEC是否起源于骨髓、骨髓修复是否是肝损伤严重程度的决定因素以及祖细胞治疗是否有益。Mct处理的雌性大鼠在窦损伤高峰时接受雄性全骨髓或CD 133+细胞输注。用荧光原位杂交法鉴定了分离的SEC中的Y染色体。骨髓抑制是由照射双下肢与腹部屏蔽诱导。未损伤肝SEC同时具有造血（CD 45、CD 33）和内皮（CD 31）标记。在Mct诱导的SOS后，骨髓来源的CD 133+祖细胞的输注取代了超过四分之一的SEC。损伤后从SEC级分回收的所有CD 133+细胞均为CD 45+。CD 133 +/45+祖细胞也能修复中央静脉内皮。Mct抑制骨髓中的CD 133 +/CD 45+祖细胞50%，并抑制循环中的CD 133 +/CD 45+祖细胞97%。辐射诱导的骨髓抑制引起SOS从亚毒性剂量的Mct，而骨髓输液在SOS的坏死阶段几乎根除SOS的组织学特征。SEC同时具有造血和内皮标志物。损伤后骨髓来源的CD 133 +/CD 45+祖细胞替代SEC和中央静脉内皮细胞。对骨髓祖细胞的毒性损害了修复，并有助于SOS的发病机制，而及时输注骨髓具有治疗益处。
Damage to hepatic sinusoidal endothelial cells (SEC) initiates sinusoidal obstruction syndrome (SOS), which is most commonly a consequence of myeloablative chemo-irradiation or ingestion of pyrrolizidine alkaloids such as monocrotaline (Mct). This study examines whether SEC are of bone marrow origin, whether bone marrow repair can be a determinant of severity of liver injury and whether treatment with progenitor cells is beneficial. Mct-treated female rats received infusion of male whole bone marrow or CD133+ cells at the peak of sinusoidal injury. The y-chromosome was identified in isolated SEC by fluorescent in situ hybridization. Bone marrow suppression was induced by irradiation of both lower extremities with shielding of the abdomen. SEC in uninjured liver have both hematopoietic (CD45, CD33) and endothelial (CD31) markers. After Mct-induced SOS, infusion of bone marrow derived CD133+ progenitor cells replaces more than one-quarter of SEC. All CD133+ cells recovered from the SEC fraction after injury are CD45+. CD133+/45+ progenitors also repaired central vein endothelium. Mct suppresses CD133+/CD45+ progenitors in bone marrow by 50% and in the circulation by 97%. Irradiation-induced bone marrow suppression elicited SOS from a sub-toxic dose of Mct, whereas infusion of bone marrow during the necrotic phase of SOS nearly eradicates histological features of SOS. SEC have both hematopoietic and endothelial markers. Bone marrow-derived CD133+/CD45+ progenitors replace SEC and central vein endothelial cells after injury. Toxicity to bone marrow progenitors impairs repair and contributes to the pathogenesis of SOS, whereas timely infusion of bone marrow has therapeutic benefit.
登录
查看更多内容
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
20.3
作者：
Shi, Q;Rafii, S;Hammond, WP
通讯作者：
Hammond, WP
DOI：
10.1073/pnas.0604203103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Bailey, Alexis S.;Willenbring, Holger;Fleming, William H.
通讯作者：
Fleming, William H.
影响因子：
3.6
作者：
Kienstra, Kirsten A.;Jackson, Kathyjo A.;Hirschi, Karen K.
通讯作者：
Hirschi, Karen K.
影响因子：
29.4
作者：
DeLeve, LD;Wang, XD;Tokes, ZA
通讯作者：
Tokes, ZA