New therapeutic approach with extracellular vesicles from stem cells for interstitial cystitis/bladder pain syndrome

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development.

MiR‐9‐enriched mesenchymal stem cells derived exosomes prevent cystitis‐induced bladder pain via suppressing TLR4/NLRP3 pathway in interstitial cystitis mice

“…As a prominent symptom of IC/BPS, bladder pain seriously affects patients' ability to perform daily work and quality of life 35 . Due to the etiology and pathogenesis of IC/BPS remains elusive, traditional treatment methods do not guarantee a satisfactory therapeutic effect and even produce detrimental side effects 36 . TLR4 activation has been found to induce and maintain a high intensity pain state in a variety of chronic pain disorders.…”

“…35 Due to the etiology and pathogenesis of IC/BPS remains elusive, traditional treatment methods do not guarantee a satisfactory therapeutic effect and even produce detrimental side effects. 36 of the foot and dorsal root ganglion induces the release of pro-inflammatory factors, which is an important factor causing postoperative pain in patients. 37 It has been reported that the peripheral blood monocytes of IC/BPS patients can induce the release of pro-inflammatory cytokines IL-1β and IL-6 under the stimulation of TLR4 agonist Lipopolysaccharide (LPS) in vitro, which is closely related to the severity of pain in patients.…”

Adipose-derived stem cell exosomes act as delivery vehicles of microRNAs in a dog model of chronic hepatitis

“…As it is well known indeed, in healthy conditions liver cell turnover is very slow, but at the same time, after 70% partial hepatectomy the liver is the only organ whose size returns to the original extent in about two weeks [20]. Despite this, in chronic and severe acute liver disease, this regenerative and replicative ability of the hepatic stem cells fails to regenerate the liver, as diffuse inflammation is present inducing increased production of matrix proteins, decreased matrix remodeling, progression to fibrosis, increase in the proportion of senescent hepatocytes (i.e., hepatocytes arrested at G1/S transition of the cell cycle) and hepatocyte death [21]. In this context, dogs primarily present with parenchymal pathologies such as hepatitis with an estimated frequency of up to 12% in the general canine population [21][22][23].…”

“…Despite this, in chronic and severe acute liver disease, this regenerative and replicative ability of the hepatic stem cells fails to regenerate the liver, as diffuse inflammation is present inducing increased production of matrix proteins, decreased matrix remodeling, progression to fibrosis, increase in the proportion of senescent hepatocytes (i.e., hepatocytes arrested at G1/S transition of the cell cycle) and hepatocyte death [21]. In this context, dogs primarily present with parenchymal pathologies such as hepatitis with an estimated frequency of up to 12% in the general canine population [21][22][23]. Considering this, in the present work we focused our attention on liver-inflamed diseases, to shift our previous study, on which we demonstrated that the use of mesenchymal stem cells in such pathology is a winning strategy [24], from a cell-based therapy to a cell-free therapy.…”

Broaden Horizons: The Advancement of Interstitial Cystitis/Bladder Pain Syndrome

“…Considering the possible immune activation and tumorigenicity of stem cell therapy, MSC-derived extracellular vesicles (MSC-EVs) might resolve this problem. Further studies are needed to assess this potential therapeutic strategy [ 125 , 126 ].…”