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

Hanchao Liu; Xinning Zhu; Xiaohui Cao; Ani Chi; Jian Dai; Zhenqing Wang; Chunhua Deng; Min Zhang

doi:10.1186/s13287-021-02579-0

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

Stem Cell Res Ther. 2021 Sep 25;12(1):514. doi: 10.1186/s13287-021-02579-0.

Authors

Hanchao Liu^#¹, Xinning Zhu^#², Xiaohui Cao^#³, Ani Chi¹, Jian Dai^{1

4}, Zhenqing Wang¹, Chunhua Deng⁵, Min Zhang⁶

Affiliations

¹ Department of Andrology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Second Road, Guangzhou, China.
² Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
³ Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, School of Medicine, Hubei Polytechnic University, 16 North Guilin Road, Huangshi, 435003, Hubei, China.
⁴ Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 51008, China.
⁵ Department of Andrology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Second Road, Guangzhou, China. dengchh@mail.sysu.edu.cn.
⁶ Department of Andrology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Second Road, Guangzhou, China. zhangm287@mail.sysu.edu.cn.

^# Contributed equally.

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 Ly6C^highCD11b⁺ 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.

Keywords: CP/CPPS; IL-1β-primed MSCs; Immunoregulation; Pain; Systemic immunity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Interleukin-1beta / pharmacology
Male
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells
Mice
Pelvic Pain* / therapy
Prostatitis* / therapy

Substances

Interleukin-1beta