Urethral Bulking With Polymethylmethacrylate Microspheres for Stress Urinary Incontinence: Tissue Persistence and Safety Studies in Miniswine

Lemperle, Gottfried; Lappin, Patrick B.; Stone, Corbett; Lemperle, Stefan M.

doi:10.1016/j.urology.2010.12.021

Cited by 13 publications

(18 citation statements)

References 26 publications

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“…More recent studies have come to a similar conclusion. Lemperle used a swine model to show that microspheres of polymethylmethacrylate, 40 µm in diameter, migrated to the lungs, whereas polymethylmethacrylate particles, 125 µm in diameter, did not . Similarly, Sternberg et al .…”

Section: Discussionmentioning

confidence: 97%

“…In addition to microsurgical techniques, this study describes in vivo physiology, novel hard tissue processing for histological analysis, and successful utilization of light microscopy and SEM, which allow for a comprehensive evaluation of urethral bulking agents using microparticles made of a hard material. Additional studies examining particle migration into the lymph nodes, liver, spleen and lungs using tissue dissolution, centrifugation and microscopy, as well as assessment of the metabolic and physiological function of the liver and kidneys, need to be carried out . This will address the possible effects of ions released from the beads, and confirm that there is no distant migration of entire particles or their components that might affect physiological function of the host.…”

Section: Discussionmentioning

confidence: 99%

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Rat animal model for preclinical testing of microparticle urethral bulking agents

et al. 2015

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Abbreviations & Acronyms ACB = alumina ceramic beads HA = hyaluronic acid SEM = scanning electron microscopy TNF-α = tumor necrosis factor-α UBT = urethral bulking therapy Objectives: To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. Methods: Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. Results: Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. Conclusions: The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Rat animal model for preclinical testing of microparticle urethral bulking agents

et al. 2015

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“…The main particle size in distant organs was 4 to 20µm, however, "their greatest dimension ranged from 4 to 80µm". This sole mention of an 80µm long, irregular PTEF particle in the lung caused the manufacturers of bulking agents for urinary incontinence to produce particles or microspheres larger than 100µm in diameter, which was designated the "critical particle size" (5,6).…”

Section: "Migration" Of Particlesmentioning

confidence: 99%

“…The diameter of the venous plexus around esophagus and urethra is around 80µm, which would allow falsely injected smaller particles or microspheres to swim directly to the lung [6]. The usual migration of macrophages with phagocytosed particles is towards lymph nodes or liver.…”

Section: /11mentioning

confidence: 99%

Biocompatibility of Injectable Microspheres

Lemperle¹

2018

BJSTR

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“…Stress urinary incontinence (SUI) is a common medical condition affecting approximately 30% of postpartum women and interfering with their quality of life [1,2]. It is defined as a "complaint of involuntary loss of urine upon effort or physical exertion (e.g., sporting activities), or sneezing or coughing" according to the International Continence Society (ICS) guidelines [3].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Human Adipose-Derived Stem Cell Exosomes in Stress Urinary Incontinence – An in Vitro and in Vivo Study

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: To evaluate whether local injection of exosomes derived from human adipose-derived stem cells (hADSCs) facilitates recovery of stress urinary incontinence (SUI) in a rat model. Methods: For the in vitro study, a Cell Counting Kit-8 (CCK-8) array and proteomic analysis were performed. For the in vivo study, female rats were divided into four groups: sham, SUI, adipose-derived stem cell (ADSC), and exosomes (n = 12 each). The SUI model was generated by pudendal nerve transection and vaginal dilation. Vehicle, hADSCs, or exosomes were injected into the peripheral urethra. After 2, 4, and 8 weeks, the rats underwent cystometrography and leak point pressure (LPP) testing, and tissues were harvested for histochemical analyses. Results: The CCK-8 experiment demonstrated that ADSC-derived exosomes could enhance the growth of skeletal muscle and Schwann cell lines in a dose-dependent manner. Proteomic analysis revealed that ADSC-derived exosomes contained various proteins of different signaling pathways. Some of these proteins are associated with the PI3K-Akt, Jak-STAT, and Wnt pathways, which are related to skeletal muscle and nerve regeneration and proliferation. In vivo experiments illustrated that rats of the exosome group had higher bladder capacity and LPP, and had more striated muscle fibers and peripheral nerve fibers in the urethra than rats of the SUI group. Both urethral function and histology of rats in the exosome group were slightly better than those in the ADSC group. Conclusions: Local injection of hADSC-derived exosomes improved functional and histological recovery after SUI.

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Urethral Bulking With Polymethylmethacrylate Microspheres for Stress Urinary Incontinence: Tissue Persistence and Safety Studies in Miniswine

Cited by 13 publications

References 26 publications

Rat animal model for preclinical testing of microparticle urethral bulking agents

Rat animal model for preclinical testing of microparticle urethral bulking agents

Biocompatibility of Injectable Microspheres

Therapeutic Potential of Human Adipose-Derived Stem Cell Exosomes in Stress Urinary Incontinence – An in Vitro and in Vivo Study

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