A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.
A physiologically based kinetic model for elucidating the in vivo distribution of administered mesenchymal stem cells.
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DOI：
10.1038/srep22293
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发表时间：
2016-02-29
影响因子：
4.6
通讯作者：
Roberts MS
中科院分区：
文献类型：
--
作者：
Wang H;Liang X;Xu ZP;Crawford DH;Liu X;Roberts MS
尽管间充质干细胞（mesenchymal stem cells，MSCs）在细胞治疗中为治疗各种疾病提供了一种有前途的工具，但对MSCs在体内的分布仍知之甚少，这阻碍了对其治疗效果的准确预测和评价。在这里，我们开发了第一个模型，以表征的生理动力学管理的MSC的基础上直接可视化的细胞时空分布的活体显微镜和评估的细胞数量，使用流式细胞术。这种基于生理学的动力学模型用多个外部数据集进行了验证，表明了潜在的途径间和种属间预测能力。我们的研究结果表明，骨髓间充质干细胞的靶向效率是由肺滞留和骨髓间充质干细胞与靶器官之间的相互作用，包括细胞停滞，消耗和释放。通过调整特定的参数，该模型可以很容易地应用于异常条件或其他类型的循环细胞，用于设计治疗方案和指导未来的实验。
Although mesenchymal stem cells (MSCs) present a promising tool in cell therapy for the treatment of various diseases, the in vivo distribution of administered MSCs has still been poorly understood, which hampers the precise prediction and evaluation of their therapeutic efficacy. Here, we developed the first model to characterize the physiological kinetics of administered MSCs based on direct visualization of cell spatiotemporal disposition by intravital microscopy and assessment of cell quantity using flow cytometry. This physiologically based kinetic model was validated with multiple external datasets, indicating potential inter-route and inter-species predictive capability. Our results suggest that the targeting efficiency of MSCs is determined by the lung retention and interaction between MSCs and target organs, including cell arrest, depletion and release. By adapting specific parameters, this model can be easily applied to abnormal conditions or other types of circulating cells for designing treatment protocols and guiding future experiments.