Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100039, People's Republic of China.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, People's Republic of China.
Int J Nanomedicine. 2020 Jun 17;15:4311-4324. doi: 10.2147/IJN.S254635. eCollection 2020.
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.
In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap-FFG) 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.
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.
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.
通过在体内提供具有特殊生物活性成分的干细胞微环境，合成生物材料在基于干细胞的组织再生方面取得了逐步成功，方法是增强移植细胞的植入和存活。具有影响细胞行为的生物活性基序和调节支架稳定性的 D 型氨基酸的设计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可能至关重要。
在这项研究中，我们将萘（Nap）共价连接到短 D 型肽（Nap-FFG）和胰岛素样生长因子-1（IGF-1C）的 C 结构域上，作为功能性水凝胶支架，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（AKI）模型中的治疗效率。
自组装肽被约束成经典的β-折叠结构并表现出水凝胶特性。我们的结果表明，这种水凝胶对 IGF-1 受体表现出更高的亲和力。此外，β-IGF-1C 水凝胶和 hP-MSCs 的共移植有助于损伤后内源性再生，并在小鼠 AKI 模型中促进血管生成，从而恢复肾功能。
该水凝胶可为 hP-MSCs 提供有利的生态位，并通过促进细胞存活和血管生成来挽救 AKI 模型中的肾功能。总之，通过将所需的功能基团共价连接到 D 型肽上来创建功能性水凝胶，自组装β-折叠肽水凝胶可以作为组织工程和干细胞治疗的有前途的平台。
