Limited accuracy of transurethral and periurethral intrasphincteric injections of cellular suspension

Burdzińska, Anna; Dybowski, Bartosz; Zarychta-Wiśniewska, Weronika; Kulesza, Agnieszka; Hawryluk, Jakub; Graczyk-Jarzynka, Agnieszka; Kaupa, Patryk; Gajewski, Zdzisław; Pączek, Leszek

doi:10.1002/nau.23522

Cited by 15 publications

(18 citation statements)

References 17 publications

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“…Recently, two preclinical studies in large animal models of SUI treatment provided evidence that transurethral injections of cells failed to precisely deposit the cells at the tissue targeted. 15,21 In about half of the samples investigated, full penetration of the needle through the urethra was noticed resulting in total loss or misplacement of the cells on the outer rim of the urethra. 15 Unnoticed and unintended misplacement of the cell suspension may contribute to the various outcomes of SUI cell therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Among other technical points, proof‐of‐precise cell injection in the urethral sphincter and verification of cell viability and functional activity during follow‐up is a challenge in a clinical situation. Recently, two preclinical studies in large animal models of SUI treatment provided evidence that transurethral injections of cells failed to precisely deposit the cells at the tissue targeted . In about half of the samples investigated, full penetration of the needle through the urethra was noticed resulting in total loss or misplacement of the cells on the outer rim of the urethra .…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Such a precision of cell injection by needle requires exceptional skills, as the physician has only limited estimation of depth of needle penetration, especially when the urethra is moving during the procedure. Imaging of the urethra during the procedure by ultrasound and mechanical devices to control protrusion improve the situation considerably [13,15,16], but do not give sufficient clues to whether the needle is pointing towards the delicate sphincter complex or fully penetrating the urethra [11,17].…”

Section: Introductionmentioning

confidence: 99%

Rapid and precise delivery of cells in the urethral sphincter complex by a novel needle‐free waterjet technology

Linzenbold

Jäger

Stoll³

et al. 2020

BJU International

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Objectives To investigate the therapy of stress urinary incontinence in a preclinical setting cells were injected into the urethrae of minipigs; however, cells injected by William’s needle were frequently misplaced or lost; thus, we investigated if needle‐free cell injections using a novel waterjet technology facilitates precise injections in the urethral sphincter complex. Materials and Methods Porcine adipose tissue‐derived stromal cells (pADSCs) were isolated from boars, expanded, labelled, and injected in the sphincter of female pigs by waterjet employing two different protocols. After incubation for 15 min or 3 days, the urethrae of the pigs were examined. Injected cells were visualised by imaging and fluorescence microscopy of tissue sections. DNA of injected male cells was verified by polymerase chain reaction (PCR) of the sex‐determining region (SRY) gene. Cell injections by William’s needle served as controls. Results The new waterjet technology delivered pADSCs faster and with better on‐site precision than the needle injections. Bleeding during or after waterjet injection or other adverse effects, such as swelling or urinary retention, were not observed. Morphologically intact pADSCs were detected in the urethrae of all pigs treated by waterjet. SRY‐PCR of chromosomal DNA and detection of recombinant green fluorescent protein verified the injection of viable cells. In contrast, three of four pigs injected by William’s needle displayed no or misplaced cells. Conclusion Transurethral injection of viable pADSCs by waterjet is a simple, fast, precise, and yet gentle new technology. This is the first proof‐of‐principle concept study providing evidence that a waterjet injects intact cells exactly in the tissue targeted in a preclinical in vivo situation. To further explore the clinical potential of the waterjet technology longer follow‐up, as well as incontinence models have to be studied.

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“…The cost-effectiveness of urethral bulking agents compared to sling surgery was doubted during a longer follow-up period of 15 months. Burdzinska and colleagues compared the accuracy between the transurethral and periurethral route of intrasphincteric injections of autologous cellular suspensions in goats [17]. Their investigation revealed that 2/3 of all injections could be located in the urethral wall, while less than 1/5 were found inside EUS muscle structures.…”

Section: Discussionmentioning

confidence: 99%

Feasibility, technique and accuracy of ultrasound-guided transurethral injections into the urinary sphincter of female cadavers: proof of concept

et al. 2020

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Background The injection of muscle precursor cells (MPC) into the external urinary sphincter muscle (EUS) is a promising therapeutic option for regenerative treatment of stress urinary incontinence (SUI). The objective of the present project was to conduct a pre-clinical trial to investigate the feasibility and accuracy of ultrasound (US) guided, transurethral injections into the EUS of female cadavers. Methods This is a prospective, anatomical, interventional and radiological cadaveric laboratory investigation. Two urologists performed transurethral US-guided injections to deliver nano-iron particles into the EUS. The intervention was performed in three unfixed, fresh female cadavers. Each cadaver received MRI before and CT as well as MRI of the pelvis after the injections. Results The precision and accumulation of nano-iron particles in the EUS was compared using a rating scale to evaluate left versus right and anterior versus posterior distribution in axial and sagittal orientation with US, MRI and CT. The accuracy of our US-guided injections into the anterior target region yielded 4 points on the rating scale. Adequate precision and accumulation of particles in the left versus right EUS were also demonstrated (3 vs. 3.33 points, respectively). Signal intensity in MRI revealed a mean ratio of 0.33 before and after injection. CT scans showed no relevant artefacts impairing the assessment. Conclusion US-guided, transurethral injection into the EUS is feasible and imaging reveals a precise accumulation in the target region. Our method provides an appropriate approach to deliver MPC in the EUS muscle for a regenerative treatment of SUI in the near future.

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Limited accuracy of transurethral and periurethral intrasphincteric injections of cellular suspension

Cited by 15 publications

References 17 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

Rapid and precise delivery of cells in the urethral sphincter complex by a novel needle‐free waterjet technology

Feasibility, technique and accuracy of ultrasound-guided transurethral injections into the urinary sphincter of female cadavers: proof of concept

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