Stem cell therapy for vocal fold regeneration after scarring: a review of experimental approaches

Abstract

This review aims at becoming a guide which will help to plan the experimental design and to choose adequate methods to assess the outcomes when testing cell-based products in the treatment of the damaged vocal folds. The requirements to preclinical trials of cell-based products remain rather hazy and dictated by the country regulations. Most parameters like the way the cells are administered, selection of the cell source, selection of a carrier, and design of in vivo studies are decided upon by each research team and may differ essentially between studies. The review covers the methodological aspects of preclinical studies such as experimental models, characterization of cell products, assessment of the study outcome using molecular, morphological and immunohistochemical analyses, as well as measuring the tissue physical properties. The unified recommendations to perform preclinical trials could significantly facilitate the translation of cell-based products into the clinical practice. Graphical abstract

Cell‐Based Outer Vocal Fold Replacement Both Treats and Prevents Vocal Fold Scarring in Rabbits

“…Yet, most preclinical work involving VF regeneration has addressed acute injuries rather than established scars. 3,4 Therefore, this study compares a COVR in a chronic scar model versus an acute injury scenario. This chronic scar model involves COVR implantation onto a previously injured VF that has had time to develop mature scar, whereas previous work has only studied COVR implantation immediately after injury.…”

“…Although prevention of VF scarring is favored over treatment, therapy is typically performed at a later stage after scarring has matured. Yet, most preclinical work involving VF regeneration has addressed acute injuries rather than established scars 3,4 . Therefore, this study compares a COVR in a chronic scar model versus an acute injury scenario.…”

“…However, clinical experience has shown that it is more difficult to reverse existing scar. 3,4 Cell-based outer vocal fold replacement (COVR) consists of human adipose-derived mesenchymal stromal cells (hASCs) embedded within a fibrin hydrogel. After exposure to epidermal growth factor, the superficial layer differentiates to epithelium, whereas the deeper mesenchymal cells remain.…”

“…Previous efforts have attempted to prevent scar formation after acute injury. However, clinical experience has shown that it is more difficult to reverse existing scar 3,4 …”

Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent

“…In vivo experiments included two consecutive blocks of hetero- and orthotopic implantations and are described below in accordance with ARRIVE guidelines. The sample size (heterotopic implantation: 500 µL of the gel without or with 5 × 10 5 cells per an animal, n = 24: 12 per condition; orthotopic implantation: 500 µL of the gel without or with 5 × 10 5 cells or 500 µL of normal saline or 500 µL of MSC suspension per an animal, n = 24: 6 per condition) was determined based on our previous experiments with similar design, and the required number of relevant assessment methods and samples were also taken into an account [ 22 , 44 ]. Inclusion and exclusion criteria were not applied due to the homogeneity of the experimental animals’ population at the start point of the study.…”