Enhanced proliferation and differentiation of retinal progenitor cells through a self-healing injectable hydrogel

Biomater Sci. 2019 May 28;7(6):2335-2347. doi: 10.1039/c8bm01579a.

Abstract

Retinal progenitor cell (RPC)-based transportation therapy is a promising strategy for repairing visual loss caused by retinal degeneration (RD) in people; however, its application is still significantly limited by the low effective delivery, proliferation and differentiation of RPCs. Herein, a self-healing injectable hydrogel (CS-Odex) based on chitosan hydrochloride (CS) and oxidized dextran (Odex) was developed via a dynamic Schiff-base linkage as a bioactive vehicle for the delivery of RPCs. Moreover, its biological effects on the RPC behaviors, including survival, proliferation and differentiation, were systematically evaluated. The CS-Odex hydrogel exhibits good biocompatibility and suitable mechanical stiffness for the growth of RPCs, and the cells can retain a high survival ratio (about 90%) with the protection of the self-healing CS-Odex hydrogels post-injection. In addition, the proliferation of RPCs in the CS-Odex hydrogels was significantly enhanced by activating the Akt and Erk pathways, especially in the hydrogel with higher CS content. Moreover, the differentiation of RPCs was improved by the CS-Odex hydrogel. Particularly, the differentiation of RPCs towards photoreceptors, the most important cell-type for RD, was elevated. Therefore, the self-healing injectable CS-Odex hydrogel would provide a promising platform for the delivery of RPCs and promote the proliferation and differentiation of RPCs towards RPC-based transplantation therapy in the future.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Chitosan / chemistry
  • Dextrans / chemistry
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hydrogels / administration & dosage
  • Hydrogels / chemistry*
  • Hydrogels / pharmacology*
  • Injections
  • MAP Kinase Signaling System / drug effects
  • Mechanical Phenomena*
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retina / cytology*
  • Schiff Bases / chemistry
  • Stem Cells / cytology*
  • Stem Cells / drug effects*

Substances

  • Dextrans
  • Hydrogels
  • Schiff Bases
  • Chitosan
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases