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可注射细胞外基质水凝胶有助于大鼠部分肾切除模型中原位细胞浸润。

Injectable extracellular matrix hydrogels contribute to native cell infiltration in a rat partial nephrectomy model.

机构信息

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

JSR-Keio University Medical and Chemical Innovation Center (JKiC), Keio University School of Medicine, Tokyo, Japan.

出版信息

J Biomed Mater Res B Appl Biomater. 2023 Jan;111(1):184-193. doi: 10.1002/jbm.b.35144. Epub 2022 Aug 8.

Abstract

Decellularized extracellular matrix (dECM) hydrogels have cytocompatibility, and are currently being investigated for application in soft tissues as a material that promotes native cell infiltration and tissue reconstruction. A dECM hydrogel has broad potential for application in organs with complex structures or various tissue injury models. In this study, we investigated the practical application of a dECM hydrogel by injecting a kidney-derived dECM hydrogel into a rat partial nephrectomy model. The prepared dECM hydrogel was adjustable in viscosity to allow holding at the excision site, and after gelation, had an elastic modulus similar to that of kidney tissue. In addition, the migration of renal epithelial cells and vascular endothelial cells embedded in dECM hydrogels was observed in vitro. Four weeks after injection of the dECM hydrogel to the partial excision site of the kidneys, infiltration of renal tubular constituent cells and native cells with high proliferative activity, as well as angiogenesis, were observed inside the injected areas. This study is the first to show that dECM hydrogels can be applied to the kidney, one of the most complex structural organs and that they can function as a scaffold to induce angiogenesis and infiltration of organ-specific renal tubular constituent cells, providing fundamental insights for further application of dECM hydrogels.

摘要

去细胞细胞外基质(dECM)水凝胶具有细胞相容性,目前正在作为一种促进固有细胞浸润和组织重建的材料,用于软组织的应用研究。dECM 水凝胶在具有复杂结构的器官或各种组织损伤模型中具有广泛的应用潜力。在这项研究中,我们通过将肾脏来源的 dECM 水凝胶注射到大鼠部分肾切除模型中,研究了 dECM 水凝胶的实际应用。制备的 dECM 水凝胶的粘度可调,可在切除部位保持,凝胶化后,其弹性模量与肾脏组织相似。此外,还观察了嵌入 dECM 水凝胶中的肾上皮细胞和血管内皮细胞的体外迁移。在将 dECM 水凝胶注射到肾脏部分切除部位的 4 周后,观察到注射部位内部有肾小管组成细胞和具有高增殖活性的固有细胞浸润以及血管生成。这项研究首次表明,dECM 水凝胶可应用于肾脏等最复杂的结构器官之一,并且可以作为一种支架来诱导血管生成和器官特异性肾小管组成细胞的浸润,为进一步应用 dECM 水凝胶提供了基础见解。

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