Feasibility of First Injection of Autologous Adipose Tissue–Derived Stromal Vascular Fraction in Human Scarred Vocal Folds

Abstract

IMPORTANCE Patients with scarred vocal folds, whether congenitally or after phonosurgery, often exhibit dysphonia that negatively affects daily life and is difficult to treat. The autologous adipose tissue-derived stromal vascular fraction (ADSVF) is a readily accessible source of cells with angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties. OBJECTIVE To evaluate the feasibility and tolerability of local injections of autologous ADSVF in patients with scarred vocal folds. DESIGN, SETTING, AND PARTICIPANTS CELLCORDES (Innovative Treatment for Scarred Vocal Cords by Local Injection of Autologous Stromal Vascular Fraction) is a prospective, open-label, single-arm, single-center, nonrandomized controlled trial with a 12-month follow-up and patient enrollment from April 1, 2016, to June 30, 2017. Eight patients with severe dysphonia attributable to vocal fold scarring associated with a congenital malformation or resulting from microsurgical sequelae (voice handicap index score >60 of 120) completed the study. Data analysis was performed from September 1, 2018, to January 1, 2019. INTERVENTIONS Injection of ADSVF into 1 or 2 vocal folds. MAIN OUTCOMES AND MEASURES The primary outcomes were feasibility and the number and severity of adverse events associated with ADSVF-based therapy. The secondary outcomes were changes in vocal assessment, videolaryngostroboscopy, self-evaluation of dysphonia, and quality of life at 1, 6, and 12 months after cell therapy. RESULTS Seven women and 1 man (mean [SD] age, 44.6 [10.4] years) were enrolled in this study. Adverse events associated with liposuction and ADSVF injection occurred; most of them resolved spontaneously. One patient received minor treatment to drain local bruising, and another experienced a minor contour defect at the liposuction site. At 12 months, the voice handicap index score was improved in all patients, with a mean (SD) improvement from baseline of 40.1 (21.5) points. Seven patients (88%) were considered to be responders, defined as improvement by 18 points or more in the voice handicap index score (the minimum clinically important difference). CONCLUSIONS AND RELEVANCE The findings suggest that autologous ADSVF injection in scarred vocal folds is feasible and tolerable. The findings require confirmation in a randomized clinical trial with a larger population.

Paracrine Effects Of Adipose-Derived Stromal/Stem Cells And Stromal Vascular Fraction In An In Vitro Fibrogenesis Model Of Human Vocal Fold Scarring

“…Several in vivo studies on animals reported significant improvements in scarred vocal folds after injection of ASC (immediately after injury or at a longer interval) in both histological and macroscopic aspects of the vocal folds [34] with an excellent tolerance of the procedure. A first clinical trial of SVF injection which enrolled 8 patients was recently reported by our group [35] suggesting a clear improvement in the majority of the vocal parameters obtained at 12 months. However, the etiology of vocal fold scarring is very heterogenous so a better understanding of the mechanisms underlying the efficacy of ASC and SVF is mandatory.…”

Achievements and Challenges in Transplantation of Mesenchymal Stem Cells in Otorhinolaryngology

“…The outcome was improved healing of scarred vocal fold, one year postoperatively [123]. Assistance Publique Hopitaux De Marseille in an open labeled single-group clinical trial enrolling eight 18 years and older patients with vocal fold scarring and dysphonia injected autologous AdSCs and reported the feasibility, safety, and efficacy of the procedure and functional measures of voice handicap index evaluated by laryngostroboscopy [124]. Lo Cicero et al confirmed use of AdSCs in patients who had undergone vocal fold lipoinjection with laryngeal hemiplegia or defects and demonstrated the therapeutic efficacy of this clinical approach and restoration of glottic competence [125].…”

Adipocyte-Based Cell Therapy in Oncology: The Role of Cancer-Associated Adipocytes and Their Reinterpretation as Delivery Platforms

“…Autologous fat tissue research has been conducted to the development of clinical trials with representative results in plastic and reconstruction surgery and regenerative medicine, especially for: breast augmentation [55,56], breast implants preventing complications [57], breast reconstruction deformities correction [56,58], soft tissue augmentation [59,60], supporting fat tissue transplantation [61], facial rejuvenation [62], burns regeneration [63] and fistulas reparation [64]. In addition, some of the clinical trials were orientated in using adipose tissue cells as treatment of various pathologic conditions: degenerative disk disease [65], ischemic disease [66], scarred vocal folds [67] and male stress urinary incontinence [68].…”