Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering

Abstract

Objective: One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds.

Methods: Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH).

Results: Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only.

Conclusions: Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.

Keywords: hyaluronic acid (HA) hydrogel; induced pluripotent stem cells (iPS); regeneration of the vocal folds; tissue engineering; vocal fold injection.