Verification of mesenchymal stem cell injection therapy for interstitial cystitis in a rat model

Chung, Jae-Wook; Chun, So Young; Lee, Eun Hye; Ha, Yun‐Sok; Lee, Jun Nyung; Song, Phil Hyun; Yoo, Eun Sang; Kwon, Tae Gyun; Chung, Sung Kwang; Park, Dong Jin

doi:10.1371/journal.pone.0226390

Cited by 19 publications

(27 citation statements)

References 41 publications

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“…Fifth, we did not perform any type of immunosuppressive study. Our study and previous studies have revealed that injection of hAFSCs in animal models developed no immune rejection against transplanted tissue 17,45,46 . Mesenchymal stem cells have the advantage of immunomodulatory properties, making these cells good candidates for xenotransplantation 47 .…”

Section: Discussionsupporting

confidence: 69%

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

Liang

Shaw

et al. 2020

Sci Rep

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The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-β1, and β3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-β1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-β1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and β3-adrenoceptor expression. Spinal cord injury (SCI) affects approximately 2.5 million people worldwide and may cause severe physical disabilities 1. Most patients with SCI develop neurogenic bladder symptoms, including overactive bladder, urinary retention, urinary tract infection, and chronic renal failure 2,3. These neurogenic bladder conditions cause altered tissue morphology, such as bladder hypertrophy 4 and fibrosis 5 , which adversely affect detrusor muscle function and result in bladder of low compliance and capacity 6. Although the effects of SCI on bladder function have been extensively studied, changes in the mechanical behaviour of the SCI bladder wall tissue have not been fully established. Abnormal expression of collagen and elastin in human bladder muscle is a histological feature characteristic of noncompliant bladder 5,7. In animal studies, bladder wall compliance is closely related to the collagen and elastin content 8,9. In addition, insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-β1) were reported to be involved in tissue remodelling and bladder wall fibrosis after SCI 9-11. Patients with chronic SCI and neurogenic bladder symptoms are currently treated with antimuscarinic medications, β3-adrenoceptor agonists, and bladder catheterization. However, these therapeutic methods are not effective and associated with adverse effects, such as dry mouth and constipation 12. Recent research efforts have focused on attempts to regenerate the injured spinal cord using cell transplantation 13. A previous study showed that the treatment of SCI with umbilical cord blood stem cells could...

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Section: Discussionsupporting

confidence: 69%

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

Liang

Shaw

et al. 2020

Sci Rep

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“…Recently, Chung et al compared the therapeutic potency of mesenchymal SCs derived from different sources—urine, bone marrow, adipose tissue, and amniotic fluid, which showed no significant differences in the regeneration of urothelium and smooth muscle. However, urine-derived stem cells showed superior anti-inflammatory properties, compared to SCs derived from other sources [ 88 ].…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

et al. 2021

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.

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“…There was a clear downregulation of inflammatory-related, apoptotic-related, oxidative stress-related, and autophagy-related markers upon injection of USCs compared to the control (untreated) group [176]. In 2019, Chung et al screened the potential of various types of ASCs, namely USCs, ADSCs, BMSCs, and AFSCs, in the recovery of UP II-mediated bladder damage in female rats [179]. In this study, all the tested stem cells showed a clear recovery capacity against UP II-induced IC compared to the control group.…”

Section: Direct Transplantationmentioning

confidence: 99%

“…Treatment with USCs resulted in an anti-inflammatory effect that was superior to that by other stem cells as shown by PCR analysis. Moreover, the authors showed that treatment with stem cells transplanted by injection into the bladder submucosa was markedly better than that via tail vein injection or transurethral instillation in terms of retaining the regenerative and anti-inflammatory potentials of the stem cells [179].…”

Section: Direct Transplantationmentioning

confidence: 99%

Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives

Dayem

Kim

Lee

et al. 2020

JCM

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic disease without definite etiology characterized by bladder-related pelvic pain. IC/BPS is associated with pain that negatively affects the quality of life. There are various therapeutic approaches against IC/BPS. However, no efficient therapeutic agent against IC/BPS has been discovered yet. Urothelium dysfunction is one of the key factors of IC/BPS-related pathogenicity. Stem cells, including adult stem cells (ASCs) and pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) and induced PSCs (iPSCs), possess the abilities of self-renewal, proliferation, and differentiation into various cell types, including urothelial and other bladder cells. Therefore, stem cells are considered robust candidates for bladder regeneration. This review provides a brief overview of the etiology, pathophysiology, diagnosis, and treatment of IC/BPS as well as a summary of ASCs and PSCs. The potential of ASCs and PSCs in bladder regeneration via differentiation into bladder cells or direct transplantation into the bladder and the possible applications in IC/BPS therapy are described in detail. A better understanding of current studies on stem cells and bladder regeneration will allow further improvement in the approaches of stem cell applications for highly efficient IC/BPS therapy.

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Verification of mesenchymal stem cell injection therapy for interstitial cystitis in a rat model

Cited by 19 publications

References 41 publications

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives

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