Bioimaging for the monitoring of the in vivo distribution of infused mesenchymal stem cells in a mouse model of the graft-versus-host reaction
Bioimaging for the monitoring of the in vivo distribution of infused mesenchymal stem cells in a mouse model of the graft-versus-host reaction
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DOI：
10.1042/cbi20100563
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发表时间：
2011-04-01
影响因子：
3.9
通讯作者：
Ryu, Kyung-Ha
中科院分区：
文献类型：
--
作者：
Joo, Sun-Young;Cho, Kyung-Ah;Ryu, Kyung-Ha
使用 MSC（间充质干细胞）进行细胞疗法可能是治疗难治性 GVHD（移植物抗宿主病）的有效方法。然而，移植后MSCs的命运和分布仍不清楚。在本研究中，开发了一种动物模型来监测 GVHD 小鼠体内 MSC 的动态分布。通过将C57BL/6供体骨髓细胞和C57BL/6 EGFP（增强型绿色荧光蛋白）脾细胞移植到经致死照射的BALB/c裸受体小鼠中建立GVHD小鼠模型。供体 MSC 从 MHC 相同的 C57BL/6 RFP（红色荧光蛋白）小鼠中获得，并在移植当天注入受体小鼠体内。通过测量生物荧光（IVIS Xenogen 系统）评估供体脾细胞 (EGFP) 和 MSC (RFP) 的体内运动。供体脾细胞和间充质干细胞首先到达肺部，然后依次到达胃肠道、淋巴结和皮肤；这些细胞的转运时间和定位位点非常相似。通过生物荧光成像评估并通过 AT（实时）-PCR 证实，在患有 GVHD 的受体小鼠中，可检测到的细胞数量随着时间的推移而减少。该生物成像系统可能有助于临床前测试和治疗策略的设计，以监测具有 GVHD 的 MSC 的动态分布。
Cell therapy using MSCs (mesenchymal stem cells) might be effective treatment for refractory GVHD (graft-versus-host disease). However, the fate and distribution of MSCs after transplantation remains unclear. In this study, an animal model was developed to monitor the dynamic distribution of MSCs in mice with GVHD. A GVHD mouse model was established by transplanting C57BL/6 donor bone marrow cells and C57BL/6 EGFP (enhanced green fluorescent protein) splenocytes into lethally irradiated BALB/c nude recipient mice. Donor MSCs were obtained from MHC-identical C57BL/6 RFP (red fluorescent protein) mice and infused into the recipient mice on the same transplantation day. In vivo movement of the donor splenocytes (EGFP) and MSCs (RFP) were evaluated by measuring the biofluorescence (IVIS Xenogen system). Donor splenocytes and MSCs reached the lungs first, and then the gastrointestinal tract, lymph nodes and skin, in that order; the transit time and localization site of these cells were very similar. In the recipient mouse with GVHD, the number of detectable cells declined with time, as assessed by biofluorescence imaging and confirmed by AT (real-time)-PCR. This bioimaging system might be useful for preclinical testing and the design of therapeutic strategies for monitoring the dynamic distribution of MSCs with GVHD.