Intratunical injection of rat-derived bone marrow mesenchymal stem cells prevents fibrosis and is associated with increased Smad7 expression in a rat model of Peyronie’s disease
Open accessAbstract
Objective: Peyronie’s disease (PD) is a fibrotic disorder of the penis, but effective treatments are lacking. Here, we observed the effects of rat-derived bone marrow mesenchymal stem cells (BMSCs) injection in the active phase and chronic phase in a rat model of PD, and the possible mechanism was analysed with fibroblasts derived from rat penile tunica albuginea (TA). Methods: Thirty-two male Sprague-Dawley rats were divided into four groups. In sham group, the rats were injected with 50 µL of vehicle. In the PD group, the rats were injected with 50 µg TGF-β1. In the PD + BMSCs early treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 10 6 BMSCs after 1 day. In the PD + BMSCs late treatment group, the rats were injected with 50 µg TGF-β1 and injected with 1 × 10 6 BMSCs after 28 days. Twenty-seven days after the last injection, the erectile function of the rats was measured, and then, penile fibrosis was analysed by histology and western blot. In vitro, fibroblasts derived from rat penile TA were used to identify a possible antifibrotic mechanism of BMSCs, and a Smad7 expression vector was used as a positive control. Fibroblasts were pretreated with the Smad7 expression vector or BMSCs for 48 h and then activated with 10 ng/mL TGF-β1 for 24 h. Cells viability was assessed, and Smad7, collagen 3, elastase-2B and osteopontin expression levels were analysed by immunofluorescence and western blot. Furthermore, fibroblasts were transfected with Smad7 siRNA or scramble control to observe whether the effects of BMSCs could be offset. Results: Erectile function obviously improved, and fibrosis of penile TA was prevented after BMSCs treatment compared with that in the rats with PD. Furthermore, the effects of BMSCs treatment in the active phase were better than those in the chronic phase. After cocultured with BMSCs, cell viability was not affected, Smad7 expression was upregulated, and collagen 3, elastase-2B and osteopontin levels were decreased in the TGF-β1-treated fibroblasts. After transfection with Smad7 siRNA, the antifibrotic effects of BMSCs were offset. Conclusions: The antifibrotic effects of BMSCs treatment in the active phase of the PD rat model were better than those in the chronic phase. A possible mechanism of BMSCs treatment was related to increased Smad7 expression, suggesting a possible effective and safe procedure for the treatment of PD.
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Current therapeutic approaches for PD often target the fibrotic process to mitigate its impact on penile function and patient quality of life.
“Current therapeutic approaches for PD often target the fibrotic process to mitigate its impact on penile function and patient quality of life.112”
From Research advances in Peyronie's disease: a comprehensive review on genomics, pathways, phenotypic manifestation, and therapeutic targets. (2024) · cites this paper as [112]
The Introduction describes PD as a fibrotic disorder that affects quality of life, and the Results report that experimental BMSC treatment suppressed fibrosis and improved erectile-function measures in rats. But the Introduction lists current treatments without saying they often target fibrosis; it instead calls for a new treatment that inhibits or reverses fibrosis. (LLM, conf=0.78)
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Background
- Authors
- Wang, W., Ding, W., Zhang, X., Wu, S., Yu, T., Cui, X., Xie, Y., Yang, D., & Lin, C.
- Affiliations
- Qingdao University (CN)
- Corresponding author
- Yang, Diandong
- Lin, Chunhua
- Venue
- Stem Cell Research & Therapy
- Published
- 2022-07-30
- Volume
- 13
- Issue
- 1
- Pages
- 390-390
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC9338499
- OpenAlex
- W4288749642
- Cited by
- 17
- References
- 31
- Citations by year
- 2025: 1 · 2024: 13 · 2023: 3
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Stem Cell Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Taishan scholar program (Tsqn202103198)
- Natural Science Foundation of Shandong Province (ZR2019MH132)
- Yantai Key Research and Development Project (2019MSGY135, 2020MSGY079)
- Topics
- Health Sciences › Medicine › Rheumatology › Dupuytren's Contracture and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- Peyronie's disease, bone marrow mesenchymal stem cells, penile fibrosis, Smad7, TGF-β1, antifibrotic therapy, erectile function, type III collagen, osteopontin, stem cell therapy, rat model, treatment timing
- MeSH terms
- Animals, Bone Marrow Cells, Disease Models, Animal, Fibrosis, Humans, Erectile Dysfunction, Male, Pancreatic Elastase, Penile Induration, Rats, Sprague-Dawley, RNA, Small Interfering, Rats, Smad7 Protein, Osteopontin, Transforming Growth Factor beta1, Mesenchymal Stem Cells
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