New concepts in regenerative medicine approaches to the treatment of female stress urinary incontinence

Bennington, Julie; Williams, J. Koudy; Andersson, Karl‐Erik

doi:10.1097/mou.0000000000000617

Cited by 13 publications

(13 citation statements)

References 32 publications

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“…While some of them improve the sequela at least for some time [2], others have been rather disappointing [3]. Recently, cell therapies were introduced as regenerative SUI therapy, but success of cellular therapies has been quite variable in both preclinical [4–7] and clinical studies [8–10]. The reasons for the variability of success of SUI cell therapies are not fully understood, but failure to deposit the cells right at or in the urethral sphincter muscle by syringe and needle may contribute to the different outcomes.…”

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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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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show abstract

“…It occurs mainly in postmenopausal women, during pregnancy, childbirth, and low estrogen level, severely impairing their quality of life [3]. Despite the earlier emphasis on the role of fascia weakness or pelvic muscle sarcopenia/dysfunction in FSUI [4,5], now it is widely accepted that a bladder urethral sphincter dystrophy/dysfunction may be the primary cause. It is also well established that SUI prevalence is predominant in patients with type 2 diabetes (T2D) and especially with obesity (T2D/O) [6,7].…”

Section: Introductionmentioning

confidence: 99%

Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo

Kovanecz

Gelfand

Lin

et al. 2019

IJMS

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Female stress urinary incontinence (FSUI) is prevalent in women with type 2 diabetes/obesity (T2D/O), and treatment is not optimal. Autograph stem cell therapy surprisingly has poor efficacy. In the male rat model of T2D/O, it was demonstrated that epigenetic changes, triggered by long-term exposure to the dyslipidemic milieu, led to abnormal global transcriptional signatures (GTS) of genes and microRNAs (miR), and impaired the repair capacity of muscle-derived stem cells (MDSC). This was mimicked in vitro by treatment of MDSC with dyslipidemic serum or lipid factors. The current study aimed to predict whether these changes also occur in stem cells from female 12 weeks old T2D/O rats, a model of FSUI. MDSCs from T2D/O (ZF4-SC) and normal female rats (ZL4-SC) were treated in vitro with either dyslipidemic serum (ZFS) from late T2D/O 24 weeks old female Zucker fatty (ZF) rats, or normal serum (ZLS) from 24 weeks old female Zucker lean (ZL) rats, for 4 days and subjected to assays for fat deposition, apoptosis, scratch closing, myostatin, interleukin-6, and miR-GTS. The dyslipidemic ZFS affected both female stem cells more severely than in the male MDSC, with some gender-specific differences in miR-GTS. The changes in miR-GTS and myostatin/interleukin-6 balance may predict in vivo noxious effects of the T2D/O milieu that might impair autograft stem cell (SC) therapy for FSUI, but this requires future studies.

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“…Obviously, to exclude that this applies only to rat MDSC/ZF4-SC, other animal stem cells may have to be studied. However, the ultimate verification would be in key human stem cells used in therapy as autografts in diabetic/obese patients [ 1 , 2 , 3 , 20 , 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

Kovanecz

Gelfand

Sharifzad

et al. 2020

IJMS

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Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performed with stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results. We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stem cells (MDSC) were from long-term T2D/O male rats, their repair efficacy for erectile dysfunction was impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures (GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemic serum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatin overexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) from the T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O lean female rats. In the current work we studied the in vitro effects of cholesterol and Na palmitate as lipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the female dyslipidemic serum was found, but differing between both lipid factors, so that each one appears to contribute specifically to the stem cell damaging effects of dyslipidemic serum in vitro and T2D/O in vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value for MDSC damage.

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New concepts in regenerative medicine approaches to the treatment of female stress urinary incontinence

Cited by 13 publications

References 32 publications

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

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

Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence Are Damaged by In Vitro Exposure to its Dyslipidemic Serum, Predicting Inadequate Repair Capacity In Vivo

Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

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