Safety and Toxicity Evaluation of Stem Cell-Based Vocal Fold Implant in Swine.

Abstract

Background/introduction: Prior to introduction in humans, new implant technology must be thoroughly assessed with preclinical animal trials. Cell-based or cell-derived therapies undergo FDA evaluation to be granted Investigational New Drug designation prior to human trials. While data required can vary across applications, standard safety and toxicity measures are valuable. We previously described a stem cell-based vocal fold implant for reconstruction of the vibratory vocal fold. This study describes a proposed set of implant release criteria and safety and toxicity evaluation following this implantation in Yucatan minipigs.

Methods: Eight Yucatan minipigs underwent bilateral Cell-based Outer Vocal Fold Replacement (COVR) containing multipotent human adipose stem cells. Perioperative corticosteroids and antibiotics were administered, but no chronic immunosuppressive medications were given. As a control, three additional animals had vocal fold resection without COVR implant and underwent an identical medication regimen. The animals were monitored for 6 months, with interval blood draws to measure basic chemistry, hematologic, and liver function tests. Any adverse events were recorded.

Results: Several animals demonstrated minor serologic findings outside of the defined normal range, but none demonstrated severe abnormalities. Adverse events included skin wound dehiscence in two animals and gastrointestinal symptoms accompanied by a temporary behavior change. All adverse events resolved following empiric treatment. Histologic examination demonstrated varying degrees of local immune response.

Conclusions: Hematologic and metabolic safety monitoring has thus far demonstrated no serious toxicity after xenograft vocal fold implantation in immunocompetent swine. Adverse events related to surgical complications are reported.

Level of evidence: N/A.