IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity

Abstract

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs. Methods By establishing a CP/CPPS mouse model and pretreating MSCs with the cytokine interleukin-1β (IL-1β), we studied the IL-1β-primed MSC immunoregulatory ability and targeted migration ability in vitro and in CP/CPPS mice. Results IL-1β levels significantly increased in the prostate tissue and serum of experimental autoimmune prostatitis (EAP) mice. Pretreatment with IL-1β enhanced the immunomodulatory potential and targeted migration of MSCs in vitro. Furthermore, intravenous infusion of IL-1β-primed MSCs dampened inflammation in prostate tissues and alleviated hyperalgesia in EAP mice. The infused MSCs inhibited monocyte infiltration and promoted regulatory T lymphocyte formation in prostate tissue, thus remodeling the local environment. Surprisingly, IL-1β-primed MSCs exhibited improved accumulation in the spleen but not in prostate tissue. Accordingly, infused MSCs reshaped systemic immunity by reducing the proportion of Ly6ChighCD11b+ monocytes and boosting the proportion of CD4+Foxp3+ regulatory T lymphocytes in the spleen and lung. Inflammatory chemokine (C–C motif) ligand 2 (CCL2) decreased through the downregulation of the NF-κB and JNK/MAPK pathways by inflammatory resolution via MSCs infusion to alleviate pain. Conclusion In summary, IL-1β-primed MSCs restored systemic immunologic homeostasis to alleviate CP/CPPS by modulating systemic immunity. These findings provide a novel strategy to boost the therapeutic effects of MSC-based therapy for CP/CPPS and reveal the essential role of systematic immunity in the treatment of CP/CPPS with MSC infusion.

Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis

“…Our previous study has shown that proper pretreatment enhanced the therapeutic effect of MSCs by regulating anti-inflammatory agents in the exosome [ 38 ]. On the other hand, MSCs exert a beneficial effect indirectly by modulating the function of neighboring immune cells [ 39 ]. Since the number of cells for injection is limited and the excess of MSCs may cause thrombosis, the engraftment rate of MSCs documented in injured areas is crucial.…”

Ningmitai capsules have anti-inflammatory and pain-relieving effects in the chronic prostatitis/chronic pelvic pain syndrome mouse model through systemic immunity

“…Based on our CP/CPPS model and previously published studies, we found that inflammation in the mouse prostate was more severe, and we observed higher proportions of proinflammatory CD11b + Ly6C high monocytes/macrophages in the lung, spleen, and blood of the mice. This may indicate that the systemic immunity of the mice was changed by inflammation ( Liu et al, 2021 ). As we mentioned previously, CD11b + immune cells patrol the body and play a proinflammatory or anti-inflammatory role.…”

“…The most widely accepted animal model of CP/CPPS (NOD-EAP) was established as described in the Methods section; in this model, the tissue structure of the mouse prostate changed after the model was successfully established, and a large number of inflammatory cells infiltrated the prostate (Figure 2A). According to a previously published article (Liu et al, 2021), the inflammatory score was used to assess the inflammatory state, and it was found that the prostate tissue inflammatory score was significantly increased in the EAP group (p < 0.001), but the difference in body weight between the two groups was not statistically significant (p > 0.05) (Figure 2B). Von Frey pain behavior test filaments were used to measure the pain of the mice with EAP, and we found that the response frequency was significantly increased in mice with EAP (p = 0.002) (Figure 2C).…”

“…In particular, the blood–prostate barrier can reduce the local drug concentration in the prostate, which reduces the therapeutic effect of the drug ( Xia et al, 2021 ). In vivo , immune cells can penetrate the blood–testis barrier, and the blood–prostate barrier affects local immunity and improves the resolution of chronic inflammation ( Pérez et al, 2014 ; Liu et al, 2021 ). In other words, targeting systemic immunity may influence local immunity through effects on immune cells.…”

Metabolomics Analysis Reveals the Differential Metabolites and Establishes the Therapeutic Effect Prediction Nomogram Among CP/CPPS Patients Who Respond or Do Not Respond to LiST

“…The aetiology and pathogenesis of CP/CPPS is still perplexing, and in recent years, infection, defective function of urothelial, abnormal gut microbiota, psychosocial status, alcohol abuse, and lifestyle habits have been reported as risk factors (4-7). Immune system disorders, including the imbalanced infiltration of macrophages, Treg cells, and cytokines (8)(9)(10)(11), have also been determined as the underlying causes of CP/CPPS.…”