Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder

Gilleran, Jason; Diokno, Ananias C.; Ward, Elijah; Sirls, Larry; Hasenau, Deborah; Giordano, Jennifer; Shea, Evelyn; Bartolone, Sarah N.; Lamb, Laura E.; Chancellor, Michael B.

doi:10.1007/s11255-021-02847-1

Cited by 9 publications

(17 citation statements)

References 27 publications

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“…Only one previous case report and one study examined the use of stem cells to treat underactive bladder. These data were produced by the same research group [ 8 , 13 ]. The case report describes only one patient, and the stem cells had a muscular origin.…”

Section: Discussionmentioning

confidence: 99%

“…The second study, which used cells derived from autologous muscle, reported an improvement of 83% in the patients studied, although only 69% stopped using intermittent catheterization. Moreover, in both studies, the therapy was considered safe, as there were no adverse effects, including the absence of hematuria, urological emergencies and/or infections [ 8 , 13 ]. Nonetheless, importantly, despite being produced by the same group of researchers, these studies contain no standardization in the nomenclature of the type of cell that was used.…”

Section: Discussionmentioning

confidence: 99%

“…The analyzed data included voided volume, residue, and voiding efficiency before and after CT treatment. The calculation was performed using the following formula: Bladder emptying efficiency = (Urinated volume/(Urinated volume + Residual)) × 100% [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

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Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial

et al. 2023

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Background Detrusor underactivity is a disease that can cause chronic urinary tract infection, urinary tract infection, urinary retention and kidney failure and has no effective treatment in traditional medicine. The present research evaluated the effects of cell therapy with adipose tissue-derived stem cells on the treatment of detrusor underactivity in men. Methods Nine male patients diagnosed with a clinical and urodynamic diagnosis of detrusor underactivity were evaluated and underwent two transplants via cystourethroscopy, with 2 × 106 cells/transplant, performed by intravesical injection at five points on the bladder body above the vesical trigone. Results Cell therapy increased the maximum flow from 7.22 ± 1.58 to 13.56 ± 1.17, increased the mean flow from 3.44 ± 0.74 to 5.89 ± 0.45, increased the urinated volume from 183.67 ± 49.28 to 304.78 ± 40.42 and reduced the residual volume in the uroflowmetry exam from 420.00 ± 191.41 to 118.33 ± 85.51; all of these changes were significant (p < 0.05). There were also significant increases (p < 0.05) in maximum flow (from 7.78 ± 0.76 to 11.56 ± 1.67), maximum detrusor pressure (from 20.22 ± 8.29 to 41.56 ± 5.75), urinary volume (from 244 ± 27.6 to 418.89 ± 32.73) and bladder contractility index (from 44.33 ± 4.85 to 100.56 ± 8.89) in the pressure flow study. Scores on the International Consultation on Incontinence Questionnaire decreased from 11.44 ± 1.43 to 3.78 ± 0.78 after cell therapy, which indicates an improvement in quality of life and a return to daily activities. No complications were observed in the 6-month follow-up after cell therapy. Before treatment, all patients performed approximately five intermittent clean catheterizations daily. After cell therapy, 7/9 patients (77.78%) did not need catheterizations, and the number of catheterizations for 2/9 patients (22.28%) was reduced to two catheterizations/day. Conclusions The results indicate that stem cell therapy led to improvements in voiding function. Cell therapy with adipose tissue-derived stem cells is safe and should be considered a new therapeutic option for the treatment of detrusor underactivity. Trial registration ISRCTN, ISRCTN23909398; Registered 15 March 2021—Retrospectively registered, https://doi.org/10.1186/ISRCTN23909398

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial

et al. 2023

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“…Various clinical trials have investigated the efficacy of autologous muscle- or adipose tissue-derived MSCs in urological diseases including stress urinary incontinence and detrusor underactivity. 9 , 29 Using autologous MSCs might be safer than using allogenic MSCs, but the challenges of hampered engraftment and survival of transplanted cells remain. Large-scale production of MSCs derived from adult tissues has limits in maintaining primitive function and proliferative capacities, 11 , 12 especially if the cells are obtained from tissues of an aged donor.…”

Section: Discussionmentioning

confidence: 99%

Safety of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells for Treating Interstitial Cystitis: A Phase I Study

Shin

Ryu

et al. 2022

Stem Cells Translational Medicine

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There are still no definite treatment modalities for interstitial cystitis (IC). Meanwhile, stem cell therapy is rising as potential alternative for various chronic diseases. This study aimed to investigate the safety of the clinical-grade mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs), code name MR-MC-01 (SNU42-MMSCs), in IC patients. Three female IC patients with (1) symptom duration >6 months, (2) visual pain analog scale (VAS) ≥4, and (3) one or two Hunner lesions <2 cm in-office cystoscopy within 1 month were included. Under general anesthesia, participants received cystoscopic submucosal injection of SNU42-MMSCs (2.0 × 107/5 mL) at the center or margin of Hunner lesions and other parts of the bladder wall except trigone with each injection volume of 1 mL. Follow-up was 1, 3, 6, 9, and 12 months postoperatively. Patients underwent scheduled follow-ups, and symptoms were evaluated with validated questionnaires at each visit. No SNU42-MMSCs-related adverse events including immune reaction and abnormalities on laboratory tests and image examinations were reported up to 12-month follow-up. VAS pain was temporarily improved in all subjects. No de novo Hunner lesions were observed and one lesion of the first subject was not identifiable on 12-month cystoscopy. This study reports the first clinical application of transurethral hESC-derived MSC injection in three patients with IC. hESC-based therapeutics was safe and proved to have potential therapeutic efficacy in IC patients. Stem cell therapy could be a potential therapeutic option for treating IC.

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“…The application of autologous muscle-derived mesenchymal stem cells (AMDC) has been reported in several clinical trials to treat stress urinary incontinence patients. Recently, Gilleran et al, reported the first regulatory approved clinical trial, which evaluated the safety and efficacy of intradetrusor injected AMDCs in 20 non-neurogenic DUA patients [ 29 ]. The study subjects received approximately 30 transurethral injections of 0.5 mL delivered to the bladder (125 million AMDC/15 mL).…”

Section: Discussionmentioning

confidence: 99%

A Preclinical Study of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells for Treating Detrusor Underactivity by Chronic Bladder Ischemia

Shin

Yun

et al. 2021

Stem Cell Rev and Rep

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Background The therapeutic effects of human embryonic stem cell-derived multipotent mesenchymal stem cells (M-MSCs) were evaluated for detrusor underactivity (DUA) in a rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and associated mechanisms. Methods Sixteen-week-old male Sprague–Dawley rats were divided into five groups (n = 10). The DUA groups underwent 30 bilateral repetitions of endothelial injury to the iliac arteries to induce CBI, while the sham control group underwent a sham operation. All rats used in this study received a 1.25% cholesterol diet for 8 weeks. M-MSCs at a density of 2.5, 5.0, or 10.0 × 105 cells (250 K, 500 K, or 1000 K; K = a thousand) were injected directly into the bladder 7 weeks post-injury, while the sham and DUA group were treated only with vehicle (phosphate buffer solution). One week after M-MSC injection, awake cystometry was performed on the rats. Then, the bladders were harvested, studied in an organ bath, and prepared for histological and gene expression analyses. Results CBI by iliac artery injury reproduced voiding defects characteristic of DUA with decreased micturition pressure, increased micturition interval, and a larger residual volume. The pathological DUA properties were improved by M-MSC treatment in a dose-dependent manner, with the 1000 K group producing the best efficacy. Histological analysis revealed that M-MSC therapy reduced CBI-induced injuries including bladder fibrosis, muscular loss, and apoptosis. Transplanted M-MSCs mainly engrafted as vimentin and NG2 positive pericytes rather than myocytes, leading to increased angiogenesis in the CBI bladder. Transcriptomes of the CBI-injured bladders were characterized by the complement system, inflammatory, and ion transport-related pathways, which were restored by M-MSC therapy. Conclusions Single injection of M-MSCs directly into the bladder of a CBI-induced DUA rat model improved voiding profiles and repaired the bladder muscle atrophy in a dose-dependent manner. Graphical abstract

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Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder

Abstract: doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Cited by 9 publications

References 27 publications

Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial

Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial

Safety of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells for Treating Interstitial Cystitis: A Phase I Study

A Preclinical Study of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells for Treating Detrusor Underactivity by Chronic Bladder Ischemia

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