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肾被膜下和实质内途径移植脐带间充质干细胞治疗 AKI-CKD 小鼠的疗效比较。

Comparison of the treatment efficacy of umbilical mesenchymal stem cell transplantation via renal subcapsular and parenchymal routes in AKI-CKD mice.

机构信息

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, No.28 Fuxing Road, Beijing, 100853, China.

Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, 300072, China.

出版信息

Stem Cell Res Ther. 2022 Mar 25;13(1):128. doi: 10.1186/s13287-022-02805-3.

Abstract

BACKGROUND

Mesenchymal stem cells (MSCs) have emerged as a promising cell-based therapy for acute kidney injury (AKI). However, the optimal route of MSC transplantation remains controversial, and there have been no comparisons of the therapeutic benefits of MSC administration through different delivery routes.

METHODS

In this study, we encapsulated MSCs into a collagen matrix to help achieve local MSC retention in the kidney and assessed the survival of MSCs in vitro and in vivo. After transplanting collagen matrix-encapsulated-MSCs (Col-MSCs) under the renal capsule or into the parenchyma using the same cell dose and suspension volume in an ischemia/reperfusion injury model, we evaluated the treatment efficacy of two local transplantation routes at different stages of AKI.

RESULTS

We found that Col-MSCs could be retained in the kidney for at least 14 days. Both local MSC therapies could reduce tubular injury, promote the proliferation of renal tubular epithelial cells on Day 3 and alleviate renal fibrosis on Day 14 and 28. MSC transplantation via the subcapsular route exerts better therapeutic effects for renal functional and structural recovery after AKI than MSC administration via the parenchymal route.

CONCLUSIONS

Subcapsular MSC transplantation may be an ideal route of MSC delivery for AKI treatment, and collagen I can provide a superior microenvironment for cell-cell and cell-matrix interactions to stabilize the retention rate of MSCs in the kidney.

摘要

背景

间充质干细胞(MSCs)已成为急性肾损伤(AKI)有前途的细胞治疗方法。然而,MSC 移植的最佳途径仍存在争议,并且尚未比较过通过不同给药途径给予 MSC 的治疗益处。

方法

在这项研究中,我们将 MSCs 包裹在胶原基质中,以帮助实现在肾脏中局部保留 MSC,并评估了 MSC 在体外和体内的存活情况。在用相同的细胞剂量和混悬液体积在缺血/再灌注损伤模型中在肾包膜下或实质内移植包裹有 MSC 的胶原基质(Col-MSCs)后,我们在 AKI 的不同阶段评估了两种局部移植途径的治疗效果。

结果

我们发现 Col-MSCs 可以在肾脏中保留至少 14 天。局部 MSC 治疗均可减轻肾小管损伤,在第 3 天促进肾小管上皮细胞的增殖,并在第 14 天和第 28 天减轻肾纤维化。与通过实质内途径给予 MSC 相比,通过肾包膜下途径给予 MSC 可更好地促进 AKI 后肾功能和结构的恢复。

结论

肾包膜下 MSC 移植可能是 AKI 治疗中 MSC 递送的理想途径,而 I 型胶原可为细胞-细胞和细胞-基质相互作用提供优越的微环境,从而稳定 MSC 在肾脏中的保留率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/202c/8953025/ff614e9e5cec/13287_2022_2805_Fig1_HTML.jpg

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