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

Int J Nanomedicine. 2020 Jun 17:15:4311-4324. doi: 10.2147/IJN.S254635. eCollection 2020.

Abstract

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

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / physiopathology
  • Animals
  • Biocompatible Materials / chemistry
  • Cell Survival
  • Female
  • Fibrosis
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hydrogels / chemical synthesis
  • Hydrogels / chemistry*
  • Insulin-Like Growth Factor I / chemistry*
  • Kidney / pathology
  • Kidney / physiopathology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mice, Transgenic
  • Neovascularization, Physiologic
  • Peptides / chemistry*
  • Placenta / cytology
  • Pregnancy
  • Protein Conformation, beta-Strand
  • Protein Domains

Substances

  • Biocompatible Materials
  • Hydrogels
  • IGF1 protein, human
  • Peptides
  • Insulin-Like Growth Factor I

Grants and funding

This research was partially supported by National Key R&D Program of China (2017YFA0103203), Key Project of the National Natural Science Foundation of China (81830060), National Key R&D Program of China (2018YFA0108803), and Key Projects of Tianjin Science and Technology Support Program (18YFZCSY00010).