In vivo visualization and portally repeated transplantation of bone marrow cells in rats with liver damage
In vivo visualization and portally repeated transplantation of bone marrow cells in rats with liver damage
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DOI：
10.1089/scd.2006.0086
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发表时间：
2007-04-01
影响因子：
4
通讯作者：
Kitajima, Masaki
中科院分区：
文献类型：
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作者：
Haga, Junko;Wakabayashi, Go;Kitajima, Masaki
最近的报道引起了人们对骨髓细胞（BMC）分化为功能性肝细胞的可行性的关注。这种增强被认为是这些细胞在肝脏疾病中的潜在临床应用所必需的。本研究旨在测定移植的BMCs的动力学，并评价重复骨髓移植（BMT）在四氯化碳诱导的大鼠肝损伤模型中的作用。使用从绿色荧光蛋白（GFP）转基因（Tg）大鼠获得的BMC，用电荷耦合器件（CCD）照相机评估移植的BMC的早期动力学，并使用从萤火虫荧光素酶（luc）Tg大鼠获得的BMC，用体内成像系统（IVIS）随访。我们使用门静脉输注系统进行重复BMT。使用该系统，通过外周静脉或门静脉（PV）一次或多次移植BMCs。结果表明，BMCs在受损肝脏中的积累比在完整肝脏中更多。经PV重复BMT的实验组肝纤维化程度较未接受BMT组轻，白蛋白染色可见大量白蛋白生成细胞。注射的BMC显示在受损的肝脏中积聚。这种重复骨髓移植的策略在增加白蛋白产生细胞的数量和抑制肝纤维化方面具有潜在的临床用途。这种有益作用的组合可能有助于细胞移植治疗的益处。在本研究中证明BMT的益处可能对临床试验具有重要意义。
Recent reports have raised concerns over the feasibility of differentiating bone marrow cells (BMCs) into functional hepatocytes. Such augmentation is considered necessary for potential clinical use of these cells in liver diseases. The present investigation was designed to determine the kinetics of transplanted BMCs and evaluate the effects of repeated bone marrow transplantation (BMT) in rat models of CCl4-induced liver damage. The early kinetics of transplanted BMCs was evaluated with a charge-coupled-device (CCD) camera using BMCs obtained from green fluorescent protein (GFP) transgenic (Tg) rats and followed up with in vivo imaging system (IVIS) using BMCs obtained from firefly luciferase (luc) Tg rats. We used a portal infusion system for repeated BMT. BMCs were transplanted via a peripheral vein or the portal vein (PV) once or repeatedly using this system. The results revealed that BMCs accumulated more in the damaged liver than in the intact liver. In the experimental group receiving repeated BMT via the PV, the liver fibrosis was milder than that in the group not receiving BMT, and large clusters of albumin-producing cells were detected by albumin staining. The injected BMCs were shown to accumulate in the damaged liver. This strategy of repeated BMT has potential clinical use in enhancing the number of albumin-producing cells and suppressing liver fibrosis. This combination of beneficial effects may contribute to the benefits of cell transplantation therapy. Demonstration of the benefits of BMT in this study may be expected to have great significance for clinical trials.