Bone marrow mesenchymal stem cells for improving hematopoietic function: an in vitro and in vivo model. Part 2: Effect on bone marrow microenvironment.
Bone marrow mesenchymal stem cells for improving hematopoietic function: an in vitro and in vivo model. Part 2: Effect on bone marrow microenvironment.
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DOI：
10.1371/journal.pone.0026241
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
del Cañizo MC
中科院分区：
文献类型：
--
作者：
Carrancio S;Blanco B;Romo C;Muntion S;Lopez-Holgado N;Blanco JF;Briñon JG;San Miguel JF;Sanchez-Guijo FM;del Cañizo MC
本研究的目的是确定间充质干细胞 (MSC) 如何在体外和体内改善受损后的骨髓 (BM) 基质功能。分离并扩增了来自 20 名健康捐献者的人类 MSC。从 20 名 HSCT 捐献者处获得动员的选定 CD34+ 祖细胞。在体外研究中，使用依托泊苷损伤的基质模型进行长期骨髓培养（LTBMC），以测试间充质干细胞在基质汇合中的作用，分析间充质干细胞在基质层中的停留能力以及一些参与造血生态位维持的分子（SDF1、骨桥蛋白）。对于体内模型，64 名 NOD/SCID 接受者通过静脉内 (IV) 或骨内 (IB) 途径移植 CD34+ 细胞，有或没有 BM 来源的 MSC。通过 FISH 分析评估 MSC 在 BM 生态位中的定位，并通过免疫组织化学评估 SDF1 和骨桥蛋白的表达。体内研究表明，当基质损伤严重时，TP-MSC 可以驻留在依托泊苷处理的骨髓基质中，如 FISH 分析所示。骨桥蛋白和SDF1在受损基质中表达不同，添加TP-MSC后表达恢复。通过 FISH 观察到人体内 MSC 沉积在 BM 生态位内，但仅检测到 MSC，而在对侧股骨中未检测到。人MSC位于股骨内膜下区域的血管周围，表达SDF1和骨桥蛋白。总之，我们的数据表明，间充质干细胞可以恢复骨髓基质功能，并且在基质损伤较高时也可以进行移植。有趣的是，MSC 在给药部位局部检测到，但在对侧股骨中未检测到。
The aim of the present study was to determine how mesenchymal stem cells (MSC) could improve bone marrow (BM) stroma function after damage, both in vitro and in vivo. Human MSC from 20 healthy donors were isolated and expanded. Mobilized selected CD34+ progenitor cells were obtained from 20 HSCT donors. For in vitro study, long-term bone marrow cultures (LTBMC) were performed using a etoposide damaged stromal model to test MSC effect in stromal confluence, capability of MSC to lodge in stromal layer as well as some molecules (SDF1, osteopontin,) involved in hematopoietic niche maintenance were analyzed. For the in vivo model, 64 NOD/SCID recipients were transplanted with CD34+ cells administered either by intravenous (IV) or intrabone (IB) route, with or without BM derived MSC. MSC lodgement within the BM niche was assessed by FISH analysis and the expression of SDF1 and osteopontin by immunohistochemistry. In vivo study showed that when the stromal damage was severe, TP-MSC could lodge in the etoposide-treated BM stroma, as shown by FISH analysis. Osteopontin and SDF1 were differently expressed in damaged stroma and their expression restored after TP-MSC addition. Human in vivo MSC lodgement was observed within BM niche by FISH, but MSC only were detected and not in the contralateral femurs. Human MSC were located around blood vessels in the subendoestal region of femurs and expressed SDF1 and osteopontin. In summary, our data show that MSC can restore BM stromal function and also engraft when a higher stromal damage was done. Interestingly, MSC were detected locally where they were administered but not in the contralateral femur.
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影响因子：
3.7
作者：
Carrancio S;Blanco B;Romo C;Muntion S;Lopez-Holgado N;Blanco JF;Briñon JG;San Miguel JF;Sanchez-Guijo FM;del Cañizo MC
通讯作者：
del Cañizo MC
影响因子：
2.4
作者：
Horvat-Karajz, Karoly;Balogh, Zsuzsanna;Uher, Ferenc
通讯作者：
Uher, Ferenc
影响因子：
3.3
作者：
Fujita, Satoshi;Toguchida, Junya;Iwata, Hiroo
通讯作者：
Iwata, Hiroo
影响因子：
20.3
作者：
Gutiérrez, NC;García, JL;San Miguel, JF
通讯作者：
San Miguel, JF
影响因子：
20.3
作者：
Blanco, B;Pérez-Simón, JA;San Miguel, J
通讯作者：
San Miguel, J