用于追踪和定量异种移植人类干细胞的免疫组织化学工具包。
Immunohistochemical toolkit for tracking and quantifying xenotransplanted human stem cells.
作者信息
Allard Justine, Li Ké, Lopez Xavier Moles, Blanchard Stéphane, Barbot Paul, Rorive Sandrine, Decaestecker Christine, Pochet Roland, Bohl Delphine, Lepore Angelo C, Salmon Isabelle, Nicaise Charles
机构信息
Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
出版信息
Regen Med. 2014;9(4):437-52. doi: 10.2217/rme.14.26.
AIM
Biomarker-based tracking of human stem cells xenotransplanted into animal models is crucial for studying their fate in the field of cell therapy or tumor xenografting.
MATERIALS & METHODS: Using immunohistochemistry and in situ hybridization, we analyzed the expression of three human-specific biomarkers: Ku80, human mitochondria (hMito) and Alu.
RESULTS
We showed that Ku80, hMito and Alu biomarkers are broadly expressed in human tissues with no or low cross-reactivity toward rat, mouse or pig tissues. In vitro, we demonstrated that their expression is stable over time and does not change along the differentiation of human-derived induced pluripotent stem cells or human glial-restricted precursors. We tracked in vivo these cell populations after transplantation in rodent spinal cords using aforementioned biomarkers and human-specific antibodies detecting apoptotic, proliferating or neural-committed cells.
CONCLUSION
This study assesses the human-species specificity of Ku80, hMito and Alu, and proposes useful biomarkers for characterizing human stem cells in xenotransplantation paradigms.
目的
基于生物标志物追踪移植到动物模型中的人类干细胞，对于在细胞治疗或肿瘤异种移植领域研究其命运至关重要。
材料与方法
我们使用免疫组织化学和原位杂交技术，分析了三种人类特异性生物标志物的表达：Ku80、人类线粒体（hMito）和Alu。
结果
我们发现Ku80、hMito和Alu生物标志物在人类组织中广泛表达，对大鼠、小鼠或猪组织无交叉反应或交叉反应较弱。在体外，我们证明它们的表达随时间稳定，并且不会随着人源诱导多能干细胞或人类神经胶质限制前体细胞的分化而改变。我们使用上述生物标志物和检测凋亡、增殖或神经定向细胞的人类特异性抗体，在体内追踪了这些细胞群体在移植到啮齿动物脊髓后的情况。
结论
本研究评估了Ku80、hMito和Alu的人类物种特异性，并提出了用于在异种移植模式中表征人类干细胞的有用生物标志物。
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