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CD44-透明质酸相互作用在外源性间充质干细胞归巢大鼠残肾中的作用。

The role of CD44-hyaluronic acid interaction in exogenous mesenchymal stem cells homing to rat remnant kidney.

机构信息

Departments of Nephrology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.

出版信息

Kidney Blood Press Res. 2013;38(1):11-20. doi: 10.1159/000355749. Epub 2014 Jan 29.

Abstract

BACKGROUND/AIMS: The aim of our study was to reveal the role of CD44-Hyaluronic acid (HA) in the homing and improving renal function of systemically transplanted MSCs in chronic renal failure.

METHODS

First, a remnant kidney model was established in rats and the expression of HA was determined using immunohistochemistry (IHC) and western blotting. Next, chemotaxis assay using flow cytometry, and cell migration assay of MSCs were performed in vitro. Then, MSCs were transplanted into rats, thus, sprague-Dawley (SD) rats were randomly divided into sham group, 5/6 nephrectomy (5/6 Nx) group, MSC group and MSC/Anti-CD44 group (n = 8 for all groups). Migration of MSCs to the kidney in these rats was assessed by using cell tracking experiments, and tissue damage was evaluated by morphological analysis using Masson's trichrome staining and periodic acid Schiff staining.

RESULTS

HA was significantly observed in 5/6 Nx group, but not in sham group. Meanwhile, HA was discovered induced MSCs migration remarkably (p < 0.05) and anti-CD44 antibody inhibited the migration significantly (p < 0.05) in vitro. In vivo, the GFP-MSCs were observed in MSC group and the cells reduced in MSC/Anti-CD44 groups, especially, in the tubulointerstitium.

CONCLUSION

Our findings reveal that CD44-HA has the potential to induce MSCs homing to injured tissue, while its effect on the ability of MSCs, improving tissue function, is not significant.

摘要

背景/目的:本研究旨在揭示 CD44-透明质酸(HA)在系统性移植的间充质干细胞归巢和改善慢性肾衰竭肾功能中的作用。

方法

首先,通过免疫组织化学(IHC)和 Western blot 检测大鼠残肾模型中 HA 的表达。然后,通过流式细胞术进行趋化性测定和间充质干细胞的细胞迁移测定。然后,将间充质干细胞移植到大鼠体内,因此,将 Sprague-Dawley(SD)大鼠随机分为假手术组、5/6 肾切除术(5/6 Nx)组、MSC 组和 MSC/抗-CD44 组(每组 8 只)。通过细胞示踪实验评估这些大鼠中 MSC 向肾脏的迁移,通过 Masson 三色染色和过碘酸希夫染色的形态学分析评估组织损伤。

结果

HA 在 5/6 Nx 组中明显观察到,但在假手术组中未观察到。同时,HA 显著诱导 MSCs 迁移(p<0.05),抗-CD44 抗体显著抑制迁移(p<0.05)。在体内,在 MSC 组中观察到 GFP-MSCs,而在 MSC/抗-CD44 组中细胞减少,尤其是在肾小管间质中。

结论

我们的研究结果表明,CD44-HA 具有诱导 MSC 归巢到受损组织的潜力,但其对 MSC 改善组织功能的能力影响不显著。

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