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

脐带间充质干细胞肾包膜下及肾实质移植对AKI-CKD小鼠治疗效果比较

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作者:Mengjie Huang #, Duo Li #, Jianwen Chen #, Yuwei Ji, Tingyu Su, Yulan Chen, Yingjie Zhang, Yuanda Wang, Fei Li, Shang Chen, Yu Dong, Qinggang Li, Lingling Wu, Zhe Feng, Jie Wu, Li Zhang, Zongjin Li, Guangyan Cai, Xiangmei Chen

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.

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.

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.

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