Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation
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 ste...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2023/8887091 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832547997668343808 |
|---|---|
| author | Qiongqiong Gao Zhentao Gao Minzhi Su Yong Huang Chi Zhang Cuiping Li Hailun Zhan Bolong Liu Xiangfu Zhou |
| author_facet | Qiongqiong Gao Zhentao Gao Minzhi Su Yong Huang Chi Zhang Cuiping Li Hailun Zhan Bolong Liu Xiangfu Zhou |
| author_sort | Qiongqiong Gao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-89e97c35e5aa413da21bd64853194ee8 |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-89e97c35e5aa413da21bd64853194ee82025-02-03T06:42:46ZengWileyStem Cells International1687-96782023-01-01202310.1155/2023/8887091Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating NeuroinflammationQiongqiong Gao0Zhentao Gao1Minzhi Su2Yong Huang3Chi Zhang4Cuiping Li5Hailun Zhan6Bolong Liu7Xiangfu Zhou8Department of UrologyDepartment of UrologyDepartment of RehabilitationDepartment of UrologyDepartment of UrologyDepartment of Biotherapy CenterDepartment of UrologyDepartment of UrologyDepartment of UrologyInterstitial 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.http://dx.doi.org/10.1155/2023/8887091 |
| spellingShingle | Qiongqiong Gao Zhentao Gao Minzhi Su Yong Huang Chi Zhang Cuiping Li Hailun Zhan Bolong Liu Xiangfu Zhou Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation Stem Cells International |
| title | Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation |
| title_full | Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation |
| title_fullStr | Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation |
| title_full_unstemmed | Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation |
| title_short | Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation |
| title_sort | umbilical cord mesenchymal stem cells overexpressing heme oxygenase 1 promotes symptoms recovery in cystitis rats by alleviating neuroinflammation |
| url | http://dx.doi.org/10.1155/2023/8887091 |
| work_keys_str_mv | AT qiongqionggao umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT zhentaogao umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT minzhisu umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT yonghuang umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT chizhang umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT cuipingli umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT hailunzhan umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT bolongliu umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation AT xiangfuzhou umbilicalcordmesenchymalstemcellsoverexpressinghemeoxygenase1promotessymptomsrecoveryincystitisratsbyalleviatingneuroinflammation |