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Kidney extracellular matrix hydrogel enhances therapeutic potential of adipose-derived mesenchymal stem cells for renal ischemia reperfusion injury.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2020-08-06 , DOI: 10.1016/j.actbio.2020.07.056
Changcheng Zhou 1 , Liuhua Zhou 1 , Jingyu Liu 2 , Luwei Xu 1 , Zheng Xu 1 , Zaozao Chen 3 , Yuzheng Ge 4 , Feng Zhao 1 , Ran Wu 4 , Xinning Wang 4 , Nan Jiang 2 , Liang Mao 4 , Ruipeng Jia 1
Affiliation  

Stem cell-based therapy has been suggested as a promising option for the treatment of renal ischemia-reperfusion injury (IRI). However, how to efficiently deliver stem cells remains a challenge. In the present study, we firstly proposed the utilization of kidney extracellular matrix hydrogel (ECMH) as an injectable scaffold for delivering adipose-derived mesenchymal stem cells (ad-MSCs) into ischemic kidneys. A modified strategy of decellularization and gelation was introduced to prepare the ECMH, by which the bioactive ingredients were retained as much as possible. Bioluminescence living imaging and immunofluorescence revealed that ECMH could significantly elevate the retention and survival rate of transplanted ad-MSCs in damaged kidneys and reduce their escape rate to other organs, which consequently resulted to the enhanced therapeutic effect of ad-MSCs on renal IRI. Further, in vitro evidence demonstrated that ECMH could remarkably reduce the oxidative stress and apoptosis, promote the proliferation, secretion, and epithelial differentiation of ad-MSCs, as well as facilitate cell migration while acting as a sustained-release scaffold. This study establishes an effective approach to enhance the therapeutic potential of ad-MSCs for renal IRI. Our findings suggest that ECMH derived from organs or tissues would be a promising injectable scaffold for stem cell-based therapy.

Statement of significance

It remains a challenge to efficiently deliver stem cells to target tissues, which may limit the clinical application of stem cell-based therapy. In this study, we developed a modified strategy of decellularization and gelation to prepare the kidney extracellular matrix hydrogel (ECMH). In vivo and in vitro evidence indicated that the kidney ECMH could improve the retention and survival rate, as well as multiple biological functions of adipose-derived mesenchymal stem cells, thereby contributing to the histological and functional recovery of injured kidneys induced by ischemia-reperfusion. Our findings highlight the use of organs or tissues derived ECMH as a promising stem cell delivery scaffold for tissue repair.



中文翻译:

肾细胞外基质水凝胶增强了脂肪来源的间充质干细胞治疗肾脏缺血再灌注损伤的潜力。

已经提出基于干细胞的疗法是治疗肾脏缺血再灌注损伤(IRI)的有前途的选择。然而,如何有效地递送干细胞仍然是一个挑战。在本研究中,我们首先提出利用肾脏细胞外基质水凝胶(ECMH)作为可注射支架,将脂肪来源的间充质干细胞(ad-MSC)输送至缺血性肾脏。引入了改良的脱细胞和凝胶化策略以制备ECMH,从而尽可能保留生物活性成分。生物发光活体成像和免疫荧光显示,ECMH可以显着提高移植的ad-MSC在受损肾脏中的保留和存活率,并降低其向其他器官的逃逸率,因此导致ad-MSC对肾脏IRI的治疗作用增强。此外,体外证据表明,ECMH可以显着降低ad-MSC的氧化应激和凋亡,促进ad-MSC的增殖,分泌和上皮分化,并在充当缓释支架的同时促进细胞迁移。这项研究建立了一种有效的方法来增强ad-MSC对肾脏IRI的治疗潜力。我们的发现表明,源自器官或组织的ECMH对于基于干细胞的治疗将是一种有前途的可注射支架。并促进细胞迁移,同时充当缓释支架。这项研究建立了一种有效的方法来增强ad-MSC对肾脏IRI的治疗潜力。我们的发现表明,源自器官或组织的ECMH对于基于干细胞的治疗将是一种有前途的可注射支架。并促进细胞迁移,同时充当缓释支架。这项研究建立了一种有效的方法来增强ad-MSC对肾脏IRI的治疗潜力。我们的发现表明,源自器官或组织的ECMH对于基于干细胞的治疗将是一种有前途的可注射支架。

重要声明

有效地将干细胞递送至靶组织仍然是一项挑战,这可能会限制基于干细胞的疗法的临床应用。在这项研究中,我们开发了一种改良的脱细胞和凝胶化策略,以制备肾脏细胞外基质水凝胶(ECMH)。体内和体外证据表明,肾脏ECMH可以改善脂肪来源的间充质干细胞的保留和存活率,以及多种生物学功能,从而有助于缺血再灌注诱导的受损肾脏的组织学和功能恢复。我们的发现突出了使用源自ECMH的器官或组织作为有前途的干细胞递送支架进行组织修复。

更新日期:2020-09-24
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