Key Takeaways & Executive Findings
- •• This phase I/IIa trial demonstrates that autologous bone marrow-derived MSC injection combined with surgical scar resection and voice training is safe and feasible for patients with vocal fold scarring and severe dysphonia, with no serious adverse events reported up to 36 months. • The study proposes a structured post-operative voice training protocol, addressing a gap in previous MSC trials where voice training was not standardized or documented. • Preliminary efficacy outcomes suggest improvements in vocal fold function and patient-reported voice-related quality of life, supporting the potential of MSC therapy as a regenerative treatment for vocal fold scarring. • The predefined clinically relevant changes and comprehensive assessment battery provide a robust framework for future larger-scale trials in this patient population.
Abstract
Background Damage to the vocal folds can result in scarring, leading to chronic, severe voice impairments for which lasting and effective treatments are currently lacking. The aim of this clinical trial was to evaluate the safety and effectiveness of autologous bone marrow-derived Mesenchymal Stromal Cell (MSC) therapy for patients with vocal fold scarring and severe dysphonia. Additionally, the study sought to propose a post-operative voice training protocol and explore its potential role in facilitating voice improvement. Methods Eight patients with vocal fold scarring and chronic dysphonia underwent surgical scar resection and autologous MSC injection, followed by voice training. Safety was continuously monitored for up to 36 months postoperatively. Data to evaluate therapeutic efficacy was collected pre-treatment, 3 and 12 months post-treatment. Assessments included analysis of vocal fold vibrations, Phonation Threshold Pressure, and Maximum Phonation Time. Patient-reported measures were collected using the Voice Handicap Index, the Vocal Fatigue Index, and ratings of major symptoms and their impact on daily life. Treatment effectiveness was analyzed at both group and individual levels, with clinically relevant changes predefined.
1. Introduction
The vocal folds comprise three main layers: the vocalis muscle, the lamina propria, and the epithelium. The epithelium and superficial lamina propria vibrate independently of the deeper layers and the vocalis muscle. Mechanical stress, environmental factors, and pathological conditions can impair vocal fold pliability, leading to a range of voice disorders [1, 2].
Injury or damage to the vocal folds can result in scarring, causing stiff tissue that restricts lamina propria vibration and pliability, impairs vocal fold closure, and disrupts the vertical glottal mucosal wave essential for voice production [3]. Known causes include surgery, radiation therapy, phonotrauma, congenital or acquired conditions, severe inflammation, and infections. Vocal fold scarring often leads to severe dysphonia, vocal strain, and vocal fatigue [4, 5].
Behavioral voice therapy is typically the first-line treatment, aiming to balance and strengthen voice subsystems while reducing hyperfunctional compensatory behaviors. However, its effectiveness in reversing scarring is limited [4, 5]. Surgical scar resection often yields suboptimal results and may even worsen the condition [5]. Injections of biomaterials like hyaluronic acid and fat have demonstrated temporary improvements [6, 7]. Animal studies suggest that growth factor injections, such as hepatocyte or basic fibroblast growth factor, may improve vocal fold healing [8, 9]. Several clinical studies have shown promising results. For example, Mattei et al. showed significant improvement in Voice Handicap Index 12 months after injecting 8 patients suffering from vocal fold scarring with autologous stromal vascular fraction [10]. Ma et al. reported significantly improved mucosal waves and voice quality in 8 patients 12 months after repeated injections with autologous fibroblasts into the vocal fold [11].
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Erika Bergström Börlin, Ulrika Nygren, Maria Södersten, Svante Granqvist, Nadir Kadri, Ida Rasmusson Duprez, Katarina Le Blanc, Stellan Hertegård (2026). An open phase I/IIa study evaluating safety, patient-reported outcomes and voice function after surgery, local administration of mesenchymal stromal cells and voice training in patients with vocal fold scarring and dysphonia. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-026-05022-4
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Frequently Asked Questions
What is the main purpose of this clinical trial?
The trial aims to evaluate the safety and effectiveness of autologous bone marrow-derived mesenchymal stromal cell (MSC) therapy combined with surgical scar resection and voice training in patients with vocal fold scarring and severe dysphonia.
How many patients were included in the study?
Eight patients with vocal fold scarring and chronic dysphonia were enrolled in this open phase I/IIa study.
What were the key outcome measures?
Outcome measures included vocal fold vibration analysis, Phonation Threshold Pressure, Maximum Phonation Time, and patient-reported measures such as the Voice Handicap Index and Vocal Fatigue Index.
What is the significance of the post-operative voice training protocol?
The study proposes a structured post-operative voice training protocol, which was not standardized in previous MSC trials, potentially enhancing functional outcomes and providing a framework for future studies.
What are the implications for future treatment of vocal fold scarring?
The results suggest that MSC therapy is safe and feasible, with preliminary improvements in voice function, supporting further investigation as a regenerative treatment option for vocal fold scarring.
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