Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

中文翻译：

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间充质干细胞局部移植入脑后生物分布的临床前研究。

间充质干细胞（MSC）的治疗功效取决于体内的生物分布和植入。与静脉输注相比，局部移植的 MSC 的生物分布尚不完全清楚。在这里，我们对局部移植后的 MSC 进行了药代动力学 (PK) 研究。我们将人类间充质干细胞移植到免疫受损的裸鼠的大脑中。然后，我们在移植一个多月后从大脑、肺和肝脏中提取了基因组 DNA。使用定量聚合酶链反应和人 Alu 特异性引物，我们分析了移植细胞的生物分布。为了评估大脑中残留免疫反应的作用，表达胞嘧啶脱氨酶（MSC/CD）的间充质干细胞被用来消除注射部位的驻留免疫细胞。大部分 Alu 信号大多保留在注射部位，并在一周内减弱，最终在一个月后变得不可检测。第一周期间，在肺和肝脏中短暂检测到可忽略不计的信号。使用 MSC/CD 抑制注射部位附近的 Iba1 阳性小胶质细胞，延长了 Alu 信号的存在。在异种移植动物模型中进行局部移植后，人类间充质干细胞主要在注射部位附近停留有限的时间，而不会扩散到其他器官。人类间充质干细胞的移植可以在免疫受损的动物中局部引发免疫反应，而抑制常驻免疫细胞可以延长移植细胞的存在时间。我们的研究为局部移植干细胞的体内命运提供了宝贵的见解，并且局部递送可有效达到治疗神经系统疾病所需的剂量。