Potential Feasibility of Early Bone Marrow Cell Injection Into the Spleen for Creating Functional Hepatocytes
Potential Feasibility of Early Bone Marrow Cell Injection Into the Spleen for Creating Functional Hepatocytes
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DOI：
10.1097/tp.0b013e31819e0528
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发表时间：
2009-04
期刊：
影响因子：
6.2
通讯作者：
R. Misawa;J. Soeda;H. Ise;Masafumi Takahashi;K. Kubota;A. Mita;Takenari Nakata;S. Miyagawa
中科院分区：
文献类型：
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作者：
R. Misawa;J. Soeda;H. Ise;Masafumi Takahashi;K. Kubota;A. Mita;Takenari Nakata;S. Miyagawa
背景。骨髓细胞（BMC）被认为具有产生功能性肝细胞的能力，并且作为代谢性肝病的治疗方式具有一些优点。然而，BMC 来源的肝细胞 (BMDH) 的出现率较低。我们假设早期 BMC 注射对于产生 BMDH 是可行的，主要有两个原因：（1）肝脏是新生大鼠的造血器官；（2）在发生严重肝损伤之前，可以有足够的时间产生更多 BMDH。方法。我们使用 Long Evans Cinnamon (LEC) 大鼠作为受体，这是 (1) 威尔逊病和 (2) 肝癌模型。通过脾脏将表达绿色荧光蛋白的 BMC 注射到新生 LEC 大鼠中。测量 LEC 大鼠中铜蓝蛋白的氧化活性较低，以评估治疗效果。此外，我们还进行了荧光原位杂交以澄清BMDH的起源，并进行了免疫组织化学分析以确认这些BMDH是否具有恶性潜力。结果。注射后18个月，我们在接受治疗的LEC大鼠的肝脏中宏观发现了一些绿色荧光蛋白表达区域。治疗的LEC大鼠(n=7)中铜蓝蛋白的氧化活性增加，并且远高于未治疗的LEC大鼠(P=0.015)。此外，我们证实 BMDH 是通过细胞融合产生的，并且在任何肿瘤病变或胆管纤维化区域中均未检测到。结论。我们的结果表明，这种创建 BMDH 的新策略是有效且安全的。
Background. Bone marrow cells (BMCs) are believed to have the ability to generate functional hepatocytes and have some merits as a therapeutic modality for metabolic liver diseases. However, the appearance of BMC-derived hepatocytes (BMDHs) is low. We hypothesized that early BMC injection would be feasible for creating BMDHs for two main reasons: (1) the liver is a hematopoietic organ in neonatal rats and (2) it may allow sufficient time to generate more BMDHs before severe liver injury occurs. Methods. We used Long Evans Cinnamon (LEC) rats as recipients, a model of (1) Wilson disease and (2) liver carcinogenesis. Green fluorescent protein-expressing BMCs were injected into newborn LEC rats through the spleen. The oxidative activity of ceruloplasmin, which is low in LEC rats, was measured to evaluate the treatment. In addition, we performed fluorescence in situ hybridization to clarify the origin of the BMDHs and immunohistochemical analysis to confirm whether these BMDHs had malignant potential. Results. At 18 months after injection, we found some green fluorescent protein-expressing areas macroscopically in the liver of treated LEC rats. The oxidative activity of ceruloplasmin increased in treated LEC rats (n=7) and were much higher than that in untreated LEC rats (P=0.015). Moreover, we confirmed that the BMDHs were generated by cell fusion and was not detected in any of the neoplastic lesions or cholngiofibrotic regions. Conclusion. Our results suggest that this novel strategy for creating BMDHs is effective and safe.