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Objectives/hypothesisTo evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer.Study designProspective, phase I, open label, clinical trial.MethodsOropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited. All patients had swallowing impairment but were not feeding tube dependent (Functional Oral Intake Scale [FOIS] ≥ 5). Muscle tissue (50-250 mg) was harvested from the vastus lateralis and 150 × 106 AMDCs were prepared (Cook MyoSite Inc., Pittsburgh, PA). The cells were injected into four sites throughout the intrinsic tongue musculature. Participants were followed for 24 months. The primary outcome measure was safety. Secondary endpoints included objective measures on swallowing fluoroscopy, oral and pharyngeal pressure, and changes in patient-reported outcomes.ResultsTen individuals were enrolled. 100% (10/10) were male. The mean age of the cohort was 65 (±8.87) years. No serious adverse event occurred. Mean tongue pressure increased significantly from 26.3 (±11.1) to 31.8 (±9.5) kPa (P = .017). The mean penetration-aspiration scale did not significantly change from 5.6 (±2.1) to 6.8 (±1.8), and the mean FOIS did not significantly change from 5.4 (±0.5) to 4.6 (±0.7). The incidence of pneumonia was 30% (3/10) and only 10% (1/10) experienced deterioration in swallowing function throughout 2 years of follow-up. The mean eating assessment tool (EAT-10) did not significantly change from 24.1 (±5.57) to 21.3 (±6.3) (P = .12).ConclusionResults of this phase I clinical trial demonstrate that injection of 150 × 106 AMDCs into the tongue is safe and may improve tongue strength, which is durable at 2 years. A blinded placebo-controlled trial is warranted.Level of evidence3 Laryngoscope, 132:523-527, 2022.

Stress urinary incontinence (SUI) is the involuntary release of urine during sudden increases in abdominal pressures. SUI is common in women after vaginal delivery or pelvic trauma and may alter the biomechanical properties of the urethra. Thus we hypothesize that injury due to vaginal distension (VD) decreases urethral basal tone and passive stiffness. This study aimed to assess the biomechanical properties of the urethra after VD in the baseline state, where basal muscle tone and extracellular matrix (ECM) are present, and in the passive state, where inactive muscle and ECM are present. Female rat urethras were isolated in a rat model of acute SUI induced by simulated birth trauma. Our established ex vivo system was utilized, wherein we applied intraluminal static pressures ranging from 0 to 20 mmHg. Outer diameter was measured via a laser micrometer. Measurements were recorded via computer. Urethral thickness was assessed histologically. Stress-strain responses of the urethra were altered by VD. Quantification of biomechanical parameters indicated that VD decreased baseline stiffness. The passive peak incremental elastic modulus of the distal segment in VD urethras was less than for controls (1.84 [+ or -] 0.67 vs. 1.19 [+ or -] 0.70 x [10.sup.6] dyne/[cm.sup.2], respectively; P = 0.016). An increase was noted in passive low-pressure compliance values in proximal VD urethras compared with controls (9.44 [+ or -] 2.43 vs. 4.62 [+ or -] 0.60 mm[Hg.sup.-1] , respectively; P = 0.04). Biomechanical analyses suggest that VD alters urethral basal tone, proximal urethral compliance, and distal stiffness. Lack of basal smooth muscle tone, in combination with these changes in the proximal and distal urethra, may contribute to SUI induced by VD. stress urinary incontinence; sphincter; collagen

Rigorous study of the associations between urethral structural anatomy and biomechanical function is necessary to advance the understanding of the development, progression, and treatment of urethral pathologies. An ex vivo model was utilized to define the relative biomechanical contributions of the active (muscle) elements of the female urethra relative to its passive (noncontractile) elements. Whole urethras from female, adult rats were tested under a range of applied intraluminal pressures (0 to 20 mmHg) as a laser micrometer simultaneously measured midurethral outer diameter. Active tissue characterization was performed during induced contraction of either smooth muscle alone ([N.sup.[omega]]-nitro-L-arginine, phenylephrine), striated muscle alone (sodium nitroprusside, atropine, hexamethonium, acetylcholine), or during collective activation of both muscles ([N.sup.[omega]]-nitro-L-arginine, phenylephrine, acetylcholine). The subsequent collection of paired passive biomechanical responses permitted the determination of parameters related to intrinsic muscle contractile function. Activation of each muscle layer significantly influenced the biomechanical responses of the tissue. Measures of muscle responsiveness over a wide range of sustained opposing pressures indicated that an activated striated muscle component was approximately one-third as effective as activated smooth muscle in resisting tissue deformation. The maximum circumferential stress generated by the striated muscle component under these conditions was also determined to be approximately one-third of that generated by the smooth muscle (748 [+ or -] 379 vs. 2,229 [+ or -] 409 [N/m.sup.2]). he experiments quantitatively reveal the relative influence of the intrinsic urethral smooth and striated muscle layers with regard to their effect on the mechanical properties and maximum functional responses of the urethra to applied intralumenal stresses in the complete absence of extrinsic influences. smooth; striated; characterization

Despite its principal mechanical function in the storage and release of urine, the biomechanical properties of the urethra have remained largely unexplored. The purpose of this study was to develop and validate an experimental model that can be used for evaluating whole urethral tissue in such a manner. Bladder-urethral specimens were excised from halothane-anesthetized female rats and mounted at in vivo length within the experimental apparatus consisting of a tissue perfusion chamber, an adjustable fluid column, and a laser micrometer. Outer diameter measurements were made at proximal, mid, and distal axial locations in response to increases in intraluminal pressure and after addition of various muscle-responsive agents. Basal smooth muscle tone and regional variations in compliance were detected through pressure-diameter responses. Chemically evoked contractile responses were measured and correspond to regional compositions of intrinsic smooth and striated muscle components. The results presented illustrate the utility of this system, which should permit a more thorough characterization of structure-function relationships and urethral biomechanical function in relation to normal and dysfunctional tissue states. urethra; smooth; striated; muscle; biomechanics

Aims: This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI)., Methods: Adult females were randomized 2:1 to iltamiocel (150 × 10 6  cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations., Results: The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants., Conclusion: The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objectives: Lidocaine cytotoxicity has been reported in some cell types, which could affect its use as a local anesthetic in cell-based therapy. We evaluated the in vitro and in vivo effect of lidocaine on rat muscle-derived progenitor cells (MDCs)., Methods: MDCs were isolated from rat skeletal muscle and purified using the preplate technique. For in vitro tests, the MDCs underwent either 2 hours of, or continuous, exposure to lidocaine (50 microM-5 mM). After 72 hours of incubation, cell viability was measured using the methylthiazololetetrazolium assay. For the in vivo tests, periurethral injection of either phosphate-buffered saline, MDCs (1 x 10(6) cells/20 microL), or 2% lidocaine plus MDCs was performed in pudendal nerve-transected rats. The leak point pressure (LPP) was measured at 4 weeks after the injection., Results: Lidocaine concentrations of < or = 500 microM had no effect on MDCs with continuous exposure. MDCs in 1 mM lidocaine showed decreased survival and no MDCs in 5 mM lidocaine survived. With a 2-hour exposure, only MDCs in the 5-mM lidocaine group showed decreased survival. Rats with nerve transection and phosphate-buffered saline injection showed significantly lower LPPs than the controls. The LPP was restored to a significantly greater level after MDCs only or lidocaine plus MDC injection. No statistically significant difference in LPP restoration was found between the MDC-only and lidocaine plus MDC injections., Conclusions: Cytotoxicity to lidocaine was minimal at a physiologic concentration in vitro. The functional recovery of LPP by MDC treatment was not affected by lidocaine preinfiltration. Taken together, our data indicate that lidocaine can be applied as a local anesthetic in periurethral MDC injection without decreasing the efficacy of the therapy.