Human Umbilical Cord Mesenchymal Stem Cell Therapy Mitigates Interstitial Cystitis by Inhibiting Mast Cells

Abstract

Background Interstitial cystitis (IC) is a recurrent and chronic inflammatory disease that compromises patients’ quality of life. Effective treatments for IC are limited. This study aimed to evaluate the therapeutic potency of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in an IC-induced rat model and investigate the potential molecular mechanism in a mast cell model (rat basophilic leukemia cells, RBL-2H3) in treating IC in a coculture system. Material/Methods The rat model of IC was induced by cyclophosphamide (CYP). Rats were randomly divided into 3 groups: sham, IC+PBS, and IC+MSC. In the coculture system, RBL-2H3 cells were sensitized overnight to Compound 48/80 (C48/80), cocultured with UC-MSCs for 3 days, and collected for subsequent experiments. RBL-2H3 cells were randomly divided into 3 groups: sham, C48, and UC-MSCs (C48+MSC). Results The UC-MSCs marked by thymidine analog 5-ethynyl-2-deoxyuridine (EdU) were transplanted in the treatment group, and were densely distributed in the bladder. Accordingly, the conscious cystometry was measured and the bladder tissues were harvested. Compared with the sham group, the treated IC rats exhibited shorter bladder voiding intervals (307±35 vs 217±37 s; P <0.01), more integral epithelia, and less collagen fiber aggregation, infiltration and degranulation of mast cells, and inflammatory cytokines in the bladder tissue. In the coculture system, compared with the C48 group, the UC-MSC-treated RBL-2H3 cells had suppressed degranulation. Conclusions UC-MSCs treatment showed a promising therapeutic effect on treating IC in vivo and in vitro. UC-MSCs inhibit mast cell degranulation in IC and could be a potential therapeutic target to ameliorate inflammation in IC.

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“…The protein kinases Fyn, Lyn, and Syk in RBL-2H3 cells are activated in the initial stage of degranulation signaling; besides, Fyn and Lyn can further activate sphingosine kinase, and Syk mediates the degranulation of RBL-2H3 cells via the production of phosphatidylinositol triphosphate ( 47 ). Compound 48/80 is commonly used to induce the activation and degranulation of RBL-2H3 cells ( 48 ). The release rate of β-hexosaminidase and the amount of histamine released are markers used to detect the degranulation of RBL-2H3 cells ( 49 ).…”

Mesenchymal stroma/stem cells: Haematologists’ friend or foe?

“…The pathogenesis of this potentially life‐threatening complication is multifactorial, including: chemotherapy and radiotherapy used in the conditioning regimen, viruses with a high rate of replication (such as polyomavirus BK) and alloimmune effects 53 . In vitro and in vivo animal models have shown that MSCs can diminish HC through activation of Wnt pathways and inhibition of mast cell infiltration and degranulation 54,55 . Consequently, MSCs have been reported to be helpful in resolving HC in patients undergoing HSCT in several small studies 56–59 .…”

“… 53 In vitro and in vivo animal models have shown that MSCs can diminish HC through activation of Wnt pathways and inhibition of mast cell infiltration and degranulation. 54 , 55 Consequently, MSCs have been reported to be helpful in resolving HC in patients undergoing HSCT in several small studies. 56 , 57 , 58 , 59 Recent pilot studies have shown efficacy of placenta‐derived decidual stromal cells (DSCs), a unique source of MSCs, for the treatment of HC, as well as aGVHD.…”

Roles of mesenchymal stem cells and exosomes in interstitial cystitis/bladder pain syndrome

“…64 Meanwhile, MSC transplantation promotes the regeneration of impaired bladder and improves the bladder voiding function in an IC rat model by downregulating the levels of interleukin (IL)-1β, IL-6 and TNFα and inhibiting the infiltration of mast cells and the apoptosis of urothelium. 65 Xu et al 66 in MSC-based therapy on urinary control and IC after urinary bladder transplantation. 70 We have found that the anti-inflammatory and immunoregulatory capacities of MSCs are more important and widely studied after we take a panoramic view of the situation from the current studies.…”

“… 64 Meanwhile, MSC transplantation promotes the regeneration of impaired bladder and improves the bladder voiding function in an IC rat model by downregulating the levels of interleukin (IL)‐1β, IL‐6 and TNF‐α and inhibiting the infiltration of mast cells and the apoptosis of urothelium. 65 Xu et al 66 were the first to demonstrate that MSCs effectively mitigate inflammation of mast cells in the disease setting of IC/BPS. MSCs significantly improve the bladder micturition function after upregulation of antioxidants and antiapoptotic proteins, including haem oxygenase (HO)‐1, NAD(P)H quinine oxidoreductase (NQO)‐1 and B‐cell lymphoma 2 (Bcl‐2).…”