Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy

使用由 IGF-1C 结构域和 D 型肽组成的混合 β 片层肽水凝胶输送 MSCs 以治疗急性肾损伤

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作者:Hongfeng Wang #, Yuna Shang #, Xiaoniao Chen, Zhongyan Wang, Dashuai Zhu, Yue Liu, Chuyue Zhang, Pu Chen, Jie Wu, Lingling Wu, Deling Kong, Zhimou Yang, Zongjin Li, Xiangmei Chen

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.

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.

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

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.

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