In the past decades, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have sparked interest in cellular therapy due to their immunomodulatory properties. Nevertheless, the fate of hUC-MSCs in the body remains poorly understood. This study aimed to investigate the biodistribution, homing and clearance of systemically administered hUC-MSCs in healthy BALB/c mice model. hUC-MSCs were labelled with GFP-Luc2 protein, followed by characterisation with flow cytometry. Upon intravenous infusion of transduced hUC-MSCs into the healthy BALB/c mice, the cells were dynamically monitored through the bioluminescent imaging (BLI) approach. Transduction of hUC-MSCs with GFP-Luc2 not only preserved the characteristics of MSCs, but also allowed live monitoring of transduced cells in the mice model. Upon systemic administration, BLI showed that transduced hUC-MSCs first localised predominantly in the lungs of healthy BALB/c mice and mainly remained in the lungs for up to 3 days before eventually cleared from the body. At terminal sacrifice, plasma chemistry biomarkers remained unchanged except for C-peptide levels, which were significantly reduced in the hUC-MSCs group. Histopathological findings further revealed that hUC-MSCs infusion did not cause any adverse effects and toxicity to lung, liver and heart tissues. Collectively, systemically administrated hUC-MSCs was safe and demonstrated dynamic homing capacity before eventually disappearing from the body.

中文翻译：

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小鼠模型静脉注射后人脐带间充质干细胞（hUC-MSCs）的动态追踪

在过去的几十年里，人类脐带间充质干细胞（hUC-MSCs）因其免疫调节特性而引起了人们对细胞治疗的兴趣。然而，人们对 hUC-MSC 在体内的命运仍知之甚少。本研究旨在研究健康 BALB/c 小鼠模型中系统施用 hUC-MSC 的生物分布、归巢和清除情况。hUC-MSC 用 GFP-Luc2 蛋白标记，然后用流式细胞术进行表征。将转导的 hUC-MSC 静脉输注至健康 BALB/c 小鼠后，通过生物发光成像 (BLI) 方法动态监测细胞。用 GFP-Luc2 转导 hUC-MSC 不仅保留了 MSC 的特性，而且还可以在小鼠模型中实时监测转导的细胞。全身给药后，BLI 显示转导的 hUC-MSCs 首先主要定位于健康 BALB/c 小鼠的肺部，并主要在肺部保留长达 3 天，然后最终从体内清除。在终末处死时，除了 C 肽水平外，血浆化学生物标志物保持不变，而 C 肽水平在 hUC-MSC 组中显着降低。组织病理学结果进一步显示，hUC-MSCs输注不会对肺、肝和心脏组织造成任何不良影响和毒性。总的来说，系统施用的 hUC-MSC 是安全的，并且在最终从体内消失之前表现出动态归巢能力。