Engineered Bone Marrow Stem Cell-Sheets Alleviate Renal Damage in a Rat Chronic Glomerulonephritis Model.
Engineered Bone Marrow Stem Cell-Sheets Alleviate Renal Damage in a Rat Chronic Glomerulonephritis Model.
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DOI：
10.3390/ijms24043711
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发表时间：
2023-02-13
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
尽管基于间充质干细胞（MSC）的再生疗法正在开发用于治疗肾脏疾病，但细胞输送和植入仍然需要改进。细胞片层技术已被开发为一种新的细胞递送方法，以片状形式回收细胞，保留内在的细胞粘附蛋白，从而提高其移植到靶组织的效率。因此，我们假设 MSC 片材能够以高移植效率治疗性地减少肾脏疾病。当在大鼠中注射两次抗Thy 1.1抗体（OX-7）诱导慢性肾小球肾炎时，评估大鼠骨髓干细胞（rBMSC）片移植的治疗效果。使用温度响应细胞培养表面制备rBMSC片，并在第一次注射OX-7后24小时将其作为补片移植到每只大鼠的两个肾脏的表面上。 4 周时，证实了移植的 MSC 片层的保留，并且具有 MSC 片层的动物的蛋白尿、肾小球细胞外基质蛋白染色以及肾脏 TGFβ1、PAI-1、胶原蛋白 I 和纤连蛋白的产生显着减少。该治疗还改善了足细胞和肾小管损伤，WT-1、podocin 和 nephrin 减少的逆转以及 KIM-1 和 NGAL 的肾过度表达证明了这一点。此外，该治疗增强了再生因子的基因表达以及IL-10、Bcl-2和HO-1 mRNA水平，但降低了肾脏中TSP-1水平、NF-kB和NAPDH氧化酶的产生。这些结果有力地支持了我们的假设，即 MSC-片层促进 MSC 移植和功能，并通过抗细胞炎症、氧化应激和细胞凋亡的旁分泌作用有效延缓进行性肾纤维化并促进再生。
Although mesenchymal stem cell (MSC)-based regenerative therapy is being developed for the treatment of kidney diseases, cell delivery and engraftment still need to be improved. Cell sheet technology has been developed as a new cell delivery method, to recover cells as a sheet form retaining intrinsic cell adhesion proteins, which promotes its transplantation efficiency to the target tissue. We thus hypothesized that MSC sheets would therapeutically reduce kidney disease with high transplantation efficiency. When the chronic glomerulonephritis was induced by two injections of the anti-Thy 1.1 antibody (OX-7) in rats, the therapeutic efficacy of rat bone marrow stem cell (rBMSC) sheet transplantation was evaluated. The rBMSC-sheets were prepared using the temperature-responsive cell-culture surfaces and transplanted as patches onto the surface of two kidneys of each rat at 24 h after the first injection of OX-7. At 4 weeks, retention of the transplanted MSC-sheets was confirmed, and the animals with MSC-sheets showed significant reductions in proteinuria, glomerular staining for extracellular matrix protein, and renal production of TGFß1, PAI-1, collagen I, and fibronectin. The treatment also ameliorated podocyte and renal tubular injury, as evidenced by a reversal in the reductions of WT-1, podocin, and nephrin and by renal overexpression of KIM-1 and NGAL. Furthermore, the treatment enhanced gene expression of regenerative factors, and IL-10, Bcl-2, and HO-1 mRNA levels, but reduced TSP-1 levels, NF-kB, and NAPDH oxidase production in the kidney. These results strongly support our hypothesis that MSC-sheets facilitated MSC transplantation and function, and effectively retarded progressive renal fibrosis via paracrine actions on anti-cellular inflammation, oxidative stress, and apoptosis and promoted regeneration.
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影响因子：
6.2
作者：
Nishida, K;Yamato, M;Okano, T
通讯作者：
Okano, T
影响因子：
7.2
作者：
Kanzaki, Masato;Takagi, Ryo;Yamato, Masayuki
通讯作者：
Yamato, Masayuki
影响因子：
13.6
作者：
Collino, Federica;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
13.6
作者：
Mu, W;Ouyang, X;Johnson, RJ
通讯作者：
Johnson, RJ
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA