Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation

• Published in: Stem cells international 2023-11, Vol.2023, p.1-14
• Main Authors: Gao, Qiongqiong, Gao, Zhentao, Su, Minzhi, Huang, Yong, Zhang, Chi, Li, Cuiping, Zhan, Hailun, Liu, Bolong, Zhou, Xiangfu
• Format: Article
• Language: English
• Subjects: Antibodies; Bladder; Carbon dioxide; Care and treatment; Cell therapy; Cyclophosphamide; Cystitis; Cytokines; Dorsal horn; Enzyme-linked immunosorbent assay; Experiments; Fluorescent antibody technique; Genetic engineering; Health aspects; Heme; Heme oxygenase (decyclizing); Immunofluorescence; Inflammation; Injection; Mechanical properties; Mesenchymal stem cells; Nocturia; Pain; Pain perception; Penicillin; Proteins; Quality of life; Short term memory; Signal transduction; Spinal cord; Stem cell research; Stem cells; TLR4 protein; Toll-like receptors; Transplantation; Umbilical cord; Urination; Vincristine
• ISSN: 1687-966X; 1687-9678; 1687-9678
• DOI: 10.1155/2023/8887091

Interstitial cystitis/bladder pain syndrome (IC/BPS) seriously reduces the patient’s quality of life, yet current therapies only provide partial relief. In the spinal dorsal horn (SDH), neuroinflammation plays a pivotal role in the development of IC. Injection of human umbilical cord mesenchymal stem cells (hUMSCs) to reduce inflammation is an effective strategy, and heme oxygenase-1 (HO-1) exhibits anti-nociceptive effect in neuroinflammatory pain. This study aimed to test the therapeutic effects of hUMSCs overexpressing HO-1 on cyclophosphamide-induced cystitis rat model. Cystitis rats were transplanted with altered cells and then assessed for 3 weeks. A series of behavioral measurements would be trial including suprapubic mechanical allodynia, depressive-like behaviors, micturition frequency, and short-term memory function. Additionally, western blot, immunofluorescence staining, and ELISA kit test for anti-inflammation effect. HUMSCs were capable of being transduced to overexpress HO-1. Injection of hUMSCs overexpressing HO-1 was more effective than hUMSCs alone in alleviating behavioral symptoms in rats. Furthermore, hUMSCs overexpressing HO-1 inhibited the activation of glial and TLR4/p65/NLRP3 pathway, decreased the levels of pro-inflammatory cytokines in the SDH region. Surprisingly, it markedly increased anti-inflammatory cytokine IL-10, reduced MDA content, and protected GSH concentrations in local environment. Our results suggest that injecting hUMSCs overexpressing HO-1 intrathecally can significantly promote functional outcomes in cystitis rats by reducing neuroinflammation, at least, partly through downregulating TLR4/p65/NLRP3 signaling pathway in the SDH region. This cell therapy affords a new strategy for IC/BPS treatment.