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Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy.
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-06-17 , DOI: 10.2147/ijn.s254635
Hongfeng Wang 1 , Yuna Shang 2 , Xiaoniao Chen 3 , Zhongyan Wang 2 , Dashuai Zhu 4 , Yue Liu 4 , Chuyue Zhang 1 , Pu Chen 1 , Jie Wu 1 , Lingling Wu 1 , Deling Kong 2 , Zhimou Yang 2 , Zongjin Li 4 , Xiangmei Chen 1
Affiliation  

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-DFDFG) 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 β-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the β-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 β-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.

Keywords: self-assembly, β-sheet, hydrogel, D-form peptide, C domain of insulin-like growth factor, IGF-1C, mesenchymal stem cells, MSCs, acute kidney injure, AKI


中文翻译:

含有 IGF-1C 结构域和 D 型肽的混合 β-片肽水凝胶的 MSC 递送用于急性肾损伤治疗。

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,合成生物材料通过增强移植细胞的植入和存活,在基于干细胞的组织再生中取得了成功。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 型氨基酸的设计可能对于开发和优化用于干细胞治疗的自组装仿生水凝胶支架至关重要。
材料和方法:在这项研究中,我们将萘 (Nap) 共价连接到短 D 型肽 (Nap- D F DFG)和胰岛素样生长因子-1(IGF-1C)的C结构域作为功能性水凝胶支架,我们假设这种水凝胶可以提高人胎盘来源的间充质干细胞(hP-MSCs)的治疗效率) 在小鼠急性肾损伤 (AKI) 模型中。
结果:自组装肽被限制在经典的β-折叠结构中,并显示出水凝胶特性。我们的结果表明,这种水凝胶对 IGF-1 受体的亲和力增加。此外,在小鼠 AKI 模型中,β-IGF-1C 水凝胶和 hP-MSCs 的共同移植有助于损伤后的内源性再生并促进血管生成,从而导致肾功能的恢复。
结论:这种水凝胶可以为 hP-MSCs 提供有利的生态位,从而通过促进细胞存活和血管生成来拯救 AKI 模型中的肾功能。总之,通过将所需的官能团与 D 型肽共价连接以产生功能性水凝胶,自组装 β-折叠肽水凝胶可作为组织工程和干细胞治疗的有前景的平台。

关键词:自组装,β-折叠,水凝胶,D型肽,胰岛素样生长因子C结构域,IGF-1C,间充质干细胞,间充质干细胞,急性肾损伤,AKI
更新日期:2020-06-30
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