Cell Therapy Clinical Trials for Stress Urinary Incontinence: Current Status and Perspectives

Aragón, Isabel M.; Herrera-Imbroda, Bernardo; Lara, M. Fernanda

doi:10.7150/ijms.22130

Cited by 34 publications

(32 citation statements)

References 58 publications

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“…Some studies reported success. 2,14,[17][18][19] A few early reports on SUI cell therapy were published but then retracted. Some unsuccessful trials may have not been published at all, while others faced an unexpected placebo response.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, improved and new regenerative therapies are under investigation. 2 Generally, minimally invasive delivery of cells bears several challenges regarding injection precision and coverage of the target. 4 In both, preclinical and clinical studies, local application of cells is achieved in most cases by transurethral injection through a cystoscope under visual control and by using needles.…”

Section: Introductionmentioning

confidence: 99%

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A novel waterjet technology for transurethral cystoscopic injection of viable cells in the urethral sphincter complex

Jäger

Linzenbold

Fech

et al. 2019

Neurourology and Urodynamics

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Aims: In a recent preclinical study, we noticed that injection of cells in the urethral sphincter by needle through a cystoscope under visual control frequently yielded in misplacement or loss of cells. We, therefore, investigated if a needle-free waterjet device delivers viable cells under defined settings, including injection volume and pressure, fluid velocity and transportation media, precisely through the urothelium and connective tissue close to the sphincter muscle without full penetration of the sphincter apparatus. Methods: Mesenchymal stromal cells (MSCs) were prepared for needle-free waterjet injections. Upon injections into liquids cell viability and yield were investigated by trypan blue dye exclusion. Upon injection into cadaveric urethral tissue samples, cells were isolated from the urethrae and expanded to prove that this novel method delivered viable cells into the tissue. MSC injections by William's needle served as controls. Results: Waterjet injections of MSCs into isotonic cell culture medium resulted in equal or better yields of viable cells when compared with needle injections.Upon injection in urethral tissue samples, the waterjet technology facilitated fast and precise injections of viable cells through urothelial, mucosal and submucosal layers to reach the sphincter muscle. By controlling the injection pressure, loss of cells due to insufficient thrust or unintended full penetration was avoided.Conclusions: Needle-free waterjet injections deliver cells in the urethra faster and more precisely when compared with needle injections without compromising their viability. This is the first proof-of-concept study providing evidence that a waterjet transports viable cells precisely into the targeted tissue. K E Y W O R D S cell injection, cell therapy, medical technology, stress urinary incontinence, waterjet ---This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Abbreviations: E, effect = pump setting, reflects a given pressure in an open system; IPCM, improved pressure control mode; LSM, laser scanning microscope; MSC, mesenchymal stromal cells; SUI, stress urinary incontinence; UPaCS, upgraded pump and controller system (based on ERBEJET 2).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel waterjet technology for transurethral cystoscopic injection of viable cells in the urethral sphincter complex

Jäger

Linzenbold

Fech

et al. 2019

Neurourology and Urodynamics

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“…5 Post-partum damage and subsequent weakening of pelvic floor and external sphincter skeletal muscles can contribute to urinary and faecal incontinence, causing social anxiety and isolation. Incontinence affects >200 million people globally, 6,7 and places a significant economic burden ($16bn in the USA alone) on patients and national health care systems. 8,9 Patients undergoing surgical interventions such as tumour ablation, soft tissue reconstruction, or joint arthroplasty almost inevitably sustain iatrogenic muscle injuries.…”

Section: Introductionmentioning

confidence: 99%

Cell therapy to improve regeneration of skeletal muscle injuries

Qazi

Duda

Ort

et al. 2019

J cachexia sarcopenia muscle

106

128

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Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.

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“…Autologous skeletal muscle derived stem cell therapy has emerged over the last few years as a promising agent for the future. The procedure involves obtaining a skeletal muscle biopsy from the patient, and then processing this in vitro in order to obtain a sufficient quantity of myogenic cells and injecting into the urethral sphincter, transurethrally or periurethrally . Further well conducted research is required in order to guide practice.…”

Section: Resultsmentioning

confidence: 99%

“…The procedure involves obtaining a skeletal muscle biopsy from the patient, and then processing this in vitro in order to obtain a sufficient quantity of myogenic cells and injecting into the urethral sphincter, transurethrally or periurethrally. 1,36,37 Further well conducted research is required in order to guide practice. Another innovative bulking agent that has recently been introduced is a biomaterial made of a vinyl dimethyl terminated polydimethylsiloxane (PDMS) polymer Urolastic®.…”

Section: Discussionmentioning

confidence: 99%

Urethral bulking agents for female stress urinary incontinence

Hussain

Bray

2019

Neurourology and Urodynamics

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Urethral bulking agents (UBAs) to treat stress urinary incontinence was first described in the 1930s, when paraffin was used to increase urethral resistance. Since then, several agents have been introduced to the market, with varying degrees of safety, efficacy, and durability. The agents currently available include calcium hydroxyl apatite (Coaptite®), carbon coated zirconium (Durasphere®); polydimethylsiloxane elastomer (Macroplastique®); and polyacrylamide hydrogel (Bulkamid®). The latest product, PDMS‐U (Urolastic ®) is a silicone gel that polymerizes when injected. The short term efficacy of UBAs are generally encouraging; however, longer follow up results show the success rates are reduced and many women will require a repeat treatment. This review looks at the currently available UBAs, application techniques, and the clinical data on their safety and efficacy.

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Cell Therapy Clinical Trials for Stress Urinary Incontinence: Current Status and Perspectives

Cited by 34 publications

References 58 publications

A novel waterjet technology for transurethral cystoscopic injection of viable cells in the urethral sphincter complex

A novel waterjet technology for transurethral cystoscopic injection of viable cells in the urethral sphincter complex

Cell therapy to improve regeneration of skeletal muscle injuries

Urethral bulking agents for female stress urinary incontinence

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