Regulatory T cell intravitreal delivery using hyaluronan methylcellulose hydrogel improves therapeutic efficacy in experimental autoimmune uveitis

Tian Zhang, Xiongqi Han, Yajie Zhong, Hio Tong Kam, Dijie Qiao, Zilin Chen, Kannie Wai Yan Chan*, Wai Po Chong*, Jun Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

2 Citations (Scopus)

Abstract

Autoimmune uveitis refers to several intraocular inflammation conditions, which are mediated by autoreactive T cells. Regulatory T cells (Tregs) are immunosuppressive cells that have shown potential for resolving various autoimmune diseases, including uveitis. However, poor donor cell dispersion distal to the injection site and plasticity of Treg cells in an inflammatory microenvironment can present obstacles for this immunotherapy. We assessed the use of a physical blend of hyaluronan and methylcellulose (HAMC) as immunoprotective and injectable hydrogel cell delivery system to improve the efficacy of Treg-based therapy in treating experimental autoimmune uveitis (EAU). We demonstrated that the Treg-HAMC blend increased both the survival and stability of Tregs under proinflammatory conditions. Furthermore, we found that the intravitreal HAMC delivery system resulted in a two-fold increase in the number of transferred Tregs in the inflamed eye of EAU mice. Treg-HAMC delivery effectively attenuated ocular inflammation and preserved the visual function of EAU mice. It significantly decreased the number of ocular infiltrates, including the uveitogenic IFN-γ+CD4+ and IL-17+CD4+ T cells. In contrast, intravitreal injection of Treg cells without HAMC only achieved marginal therapeutic effects in EAU. Our findings suggest that HAMC may become a promising delivery vehicle for human uveitis Treg therapy.

Original languageEnglish
Article number213496
JournalBiomaterials Advances
Volume151
Early online date2 Jun 2023
DOIs
Publication statusPublished - Aug 2023

Scopus Subject Areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Biomaterials

User-Defined Keywords

  • Experimental autoimmune uveitis
  • HAMC
  • Intravitreal delivery
  • Regulatory T cell

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