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 AND 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.
Subject(s)
Cord Blood Stem Cell Transplantation/methods , Cystitis, Interstitial , Mast Cells/immunology , Umbilical Cord/cytology , Urinary Bladder , p-Methoxy-N-methylphenethylamine/pharmacology , Animals , Cell Degranulation/drug effects , Coculture Techniques/methods , Cystitis, Interstitial/immunology , Cystitis, Interstitial/therapy , Cytokines/analysis , Disease Models, Animal , Humans , Inflammation/metabolism , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Rats , Urinary Bladder/immunology , Urinary Bladder/pathology , Urinary Bladder/physiopathology , Urination/immunologyABSTRACT
In the present study we compared the effects of acute (30 min), white and illuminated open field (OF) stress on behavioral, immune and endocrine variables between rats divided into high (HR) and low (LR) responsive to novelty and in a non-divided group. It was found that OF-induced behavioral depression which was in parallel to suppression of both blood and spleen natural killer cell cytotoxicity (NKCC), large granular lymphocyte (LGL) and lymphocyte numbers occurred in stressed LR rats only. There was no significant difference in the plasma level of corticosterone (COR) and testosterone (TST) between HR and LR rats. In contrast, when the HR and LR groups were examined together (the non-divided group), no significant influence of OF stress on behavioral activity or NKCC was observed. These results emphasize that individual differences as measured by spontaneous locomotor activity play the important role for the study of the mechanisms involved in stress-induced immunomodulation and indicate that OF stress-induced behavioral depression in low reactivity animals may be accompanied by impaired defence against viral infections and neoplastic growth, which is functionally related to NKCC.
Subject(s)
Cytotoxicity Tests, Immunologic , Exploratory Behavior , Killer Cells, Natural/immunology , Motor Activity/immunology , Spleen/cytology , Spleen/immunology , Stress, Psychological/blood , Stress, Psychological/immunology , Animals , Corticosterone/blood , Cytotoxicity Tests, Immunologic/methods , Grooming , Leukocyte Count , Lymphocyte Count , Male , Rats , Rats, Wistar , Stress, Psychological/physiopathology , Testosterone/blood , Urination/immunologyABSTRACT
Behavioural studies of MHC-congenic mice and rats have focused primarily on mate choice and the ability to discriminate between strains by their urine odours, but these strains may differ in other behaviours, such as activity and ultrasonic vocalizations. Ivanyi (1978, Proc. Roy. Soc. Lord. 202, 117-158) has reviewed the physiological differences associated with the MHC, many of which could influence behaviour. We have started a systematic study of behavioural development and adult behaviour in MHC-congenic mice. A developmental test battery (growth, rate, locomotion, grooming, eye opening, ultrasonic vocalizations, etc.) was used to examine differences between C57BL/6J vs. B6-H-2bml and C57BL/10SnJ vs. B10.BR/sgSnJ mice. A test battery of spontaneous behaviours (activity, exploration, ultrasonic vocalizations, etc.) was used to examine behavioural differences between adult C57BL/6J vs. B6-H-2bml; and C57BL/10SnJ vs. B10.BR/sgSnJ mice. Differences in development and in adult behaviours between these MHC-congenic strains is discussed in relation to possible neural, endocrine and immune system differences. Future studies will compare MHC-congenic mice on levels of anxiety, sociosexual behaviour and on learning paradigms.
