Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy
Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy
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DOI：
10.2147/ijn.s254635
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发表时间：
2020-01-01
影响因子：
8
通讯作者：
Chen, Xiangmei
中科院分区：
文献类型：
--
作者：
Wang, Hongfeng;Shang, Yuna;Chen, Xiangmei
目的：通过在体内提供具有特定生物活性成分的干细胞微环境，合成生物材料已经通过增强移植细胞的植入和存活而在基于干细胞的组织再生中逐渐成功。具有影响细胞行为的生物活性基序和具有调节支架稳定性的D型氨基酸的设计对于用于干细胞治疗的自组装仿生水凝胶支架的开发和优化可能是至关重要的。在本研究中，我们将萘（Nap）共价连接到短D型肽（Nap-（D）F（D）FG）和胰岛素样生长因子-1（IGF-1C）的C结构域上，作为一种功能性水凝胶支架，我们假设这种水凝胶可以增强人胎盘间充质干细胞（hP-MSCs）在小鼠急性肾损伤（阿基）模型中的治疗效率。我们的结果表明，这种水凝胶表现出对IGF-1受体的亲和力增加。此外，共同移植的β-IGF-1C水凝胶和hP-MSCs有助于内源性再生后损伤和促进血管生成的小鼠阿基模型，导致肾功能recovery of renal function.Conclusion：这种水凝胶可以提供一个有利的生态位hP-MSCs，从而拯救肾功能阿基模型，通过促进细胞存活和血管生成。总之，通过共价连接所需的功能基团的D-型肽，以创建功能性水凝胶，自组装β-折叠肽水凝胶可以作为一个有前途的组织工程和干细胞治疗的平台。
Purpose: By providing a stem cell microenvironment with particular bioactive constituents in vivo, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. Designs with bioactive motifs to influence cell behavior and with D-form amino acids to modulate scaffold stability may be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy.Materials and Methods: In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap-(D)F(D)FG) and the C domain of insulin-like growth factor-1 (IGF-1C) as a functional hydrogel-based scaffolds, and we hypothesized that this hydrogel could enhance the therapeutic efficiency of human placenta-derived mesenchymal stem cells (hP-MSCs) in a murine acute kidney injury (AKI) model.Results: The self-assembling peptide was constrained into a classical beta-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the beta-IGF-1C hydrogel and hP-MSCs contributed to endogenous regeneration post-injury and boosted angiogenesis in a murine AKI model, leading to recovery of renal function.Conclusion: This hydrogel could provide a favorable niche for hP-MSCs and thereby rescue renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional groups to D-form peptides to create functional hydrogels, self-assembling beta-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.