Mesenchymal stem cells (MSC) offer great promise for treatment of inflammatory disorders. Cats spontaneously develop a variety of disorders that can serve as translational model for human diseases. One such disorder is chronic feline idiopathic cystitis, which closely resembles human Interstitial Cystitis/ Painful Bladder Syndrome. These cystopathies in both cats and humans are characterized by inflammatory cell infiltrate within bladder wall. Since MSC have been reported to migrate to sites of inflammation, bladder wall inflammation can potentially be targeted by MSC, whose immunomodulatory properties could beneficially affect disease expression. One of the initial steps needed to evaluate use of feline MSC, as a potential therapy is to investigate similarities between feline and human MSC in their immunomodulatory properties. We investigated expression of genes involved in MSC immunomodulation and how they react to stimulation with two cytokines INFγ and TNFα. Unstimulated MSC express similar immunomodulatory genes as human MSC except for FASL and IL10. The reaction of feline MSC to cytokine stimulation is similar to that of human MSC, including the upregulation of IDO in reaction to INFγ stimulation. Other genes upregulated by stimulation included IL-6, PD-L1 and HGF. IL-6 was also significantly upregulated at protein level after stimulation. However levels of HGF were lowered in cell culture supernatants under some conditions. Increased IDO expression was further confirmed through increase in kynurenine, a tryptophan degradation product. TNFα stimulation resulted in strong upregulation of IL-6 gene and protein expression. Interestingly PGE2 levels remained unchanged after stimulation, although basal expression of this factor was high relative to published human data. Feline MSC were also capable of blocking proliferation of activated peripheral blood mononuclear cells. Route of injection of MSC can potentially affect the efficacy of MSC therapy. To avoid pulmonary vascular trapping after IV injection we have investigated the intraperitoneal route of MSC injection, as an alternative route of MSC administration. Our studies show intraperitoneal administration of MSC is safe and associated with only mild short-term adverse effects. Reliable biomarkers are not currently available for FIC. This makes diagnosis dependent on exclusion of other lower urinary tract disorders and evaluation of patient responses difficult. We investigated urine and serum cytokine concentration as biomarkers. We have identified that FIC affected cats have increased urine concentrations of IL-6 and sFAS and increased serum IL-12, IL-18, SDF1 and FLT3. Lastly, we performed a pilot study to evaluate MSC based therapy for chronic FIC. Unfortunately, only one patient met inclusion criteria and received autologous MSC by IP injection. While reportedly showing an initial favorable response for the first 10 days, clinical signs returned and were progressive. This initial experience was very informative with regard to the many practical difficulties of assessing the effects of such a treatment in this complicated disease.
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