Single-cell transcriptomic data reveal the increase in extracellular matrix organization and antigen presentation abilities of fibroblasts and smooth muscle cells in patients with pelvic organ prolapse

Fan, Weimin; Wu, Duanqing; Zhang, Liwen; Ye, Jun; Yang, Ying; Xiaohui, Mei; Chen, Rujun

doi:10.1007/s00192-023-05539-9

Cited by 2 publications

(4 citation statements)

References 22 publications

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“…Smooth muscles play an important role in the function of the vaginal wall [ 15 ]. The content of smooth muscle cells (SMCs) in the vagina decreases with aging and is less in women with pelvic organ prolapse (POP) compared to un-affected women[ 16 – 18 ]. This decrease in smooth muscle content, organization, and composition can negatively affect vaginal tone and contractility, which are characteristic of prolapsed vaginal tissue [ 15 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…The content of smooth muscle cells (SMCs) in the vagina decreases with aging and is less in women with pelvic organ prolapse (POP) compared to un-affected women[ 16 – 18 ]. This decrease in smooth muscle content, organization, and composition can negatively affect vaginal tone and contractility, which are characteristic of prolapsed vaginal tissue [ 15 , 18 ]. This may be due to the effect of aging on the regenerative ability of muscle by reducing both stem cell pool and functionality [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…The literature supports differential expression of ECM components in women with and without POP, however, the data are not consistent. Some studies document increase in fibroblasts, collagen, and elastin fibers with aging, while others have observed poor-quality collagen or elastin fibers in women with POP[ 16 , 18 , 27 ]. Moalli et al observed an increase in collagen III in the sub-epithelium and muscular layer of the vaginal wall in patients with POP[ 20 ].…”

Section: Discussionmentioning

confidence: 99%

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Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells

Wang,

Wen,

Kim

et al. 2024

Preprint

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Background: Stem-cell-derived therapy is a promising option for tissue regeneration. Human iPSC-derived progenitors of smooth muscle cells (pSMCs) have limited proliferation and differentiation, which may minimize the risk of in vivo tumor formation while restoring smooth muscle cell deficiencies. Up to 30 % of women who suffer from recurrence of vaginal prolapse after prolapse surgery are faced with reoperation. Therefore, there is an unmet need for therapies that can restore vaginal tissue function. We hypothesize that human pSMCs can restore vaginal function in a vaginal-injury rat model. Methods: Female immune-compromised RNU rats were divided into 5 groups: intact controls (n=12), VSHAM (surgery + saline injection, n=33), and cell-injection group (surgery + cell injection using three patient pSMCs lines, n=14/cell line). The surgery, similar to what is done in vaginal prolapse surgery, involved ovariectomy, urethrolysis, and vagina injury. The vagina, urethra, bladder dome and trigone were harvested 10 weeks after surgery (5 weeks after injection). Organ bath myography was performed to evaluate the contractile function of vagina, and smooth muscle thickness was examined by tissue immunohistochemistry. Collagen I, collagen III, and elastin mRNA and protein expressions in tissues were assessed. Results: When compared to the VSHAM group, cell-injection groups showed significantly increased vaginal smooth muscle contractions induced by carbachol (groups A and C) and by KCl (group C), and significantly higher collagen I protein expression in the vagina (groups A and B). Elastin mRNA and protein expressions in the vagina did not correlate with injection group. In the urethra, mRNA expressions of collagen I, collagen III, and elastin were all significantly higher in the cell-injection groups compared to the VSHAM group. Collagen I protein expression of the urethra was also higher in the cell-injection group compared to the VSHAM group. Elastin protein expression in the urethra did not correlate with injection group. Conclusions: Human iPSC-derived pSMCs improved contractile function of the post-surgery vagina. Additionally, pSMC injection modulated collagen I, collagen III and elastin mRNA and protein expressions in the vagina and urethra. These findings suggest that pSMCs may be a possible therapy for vaginal prolapse recurrence after surgical intervention.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells

Wang,

Wen,

Kim

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…[7,8] Fibroblasts are the major cell type in the vagina wall and are the key to ECM regulation. [9] Dense connective tissues composed of vaginal wall fibroblasts (VWFs) and the secreted ECM from the pelvic floor fascia and ligaments, which lesions lead to POP. [10,11] Therefore, studying ECM degradation, proliferation, and apoptosis of VWFs helps us understand the pathogenesis of POP.…”

Section: Introductionmentioning

confidence: 99%

FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway

Li,

Zhang,

Chu

et al. 2024

J Biochem & Molecular Tox

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The occurrence of pelvic organ prolapse (POP) seriously affects women's quality of life. However, the pathogenesis of POP remains unclear. We aimed to clarify the role of Frizzled class receptor 3 (FZD3) in POP. FZD3 expression in the vaginal wall tissues was detected using immunohistochemistry, real‐time polymerase chain reaction, and western blot analysis. Then, vaginal wall fibroblasts (VWFs) were isolated from patients with POP and non‐POP, and were identified. Cell viability and apoptosis were evaluated using Cell Counting Kit‐8 and flow cytometry, respectively. Extracellular matrix (ECM) degradation was assessed by western blot analysis. The results illustrated that FZD3 was downregulated in POP. VWFs from POP had lower cell viability, ECM degradation, and higher apoptosis. Knockdown of FZD3 inhibited cell viability, ECM degradation, and promoted apoptosis of VWFs, whereas overexpression of FZD3 had opposite results. Moreover, IWP‐4 (Wingless‐type [Wnt] pathway inhibitor) reversed the role of FZD3 overexpression on biological behaviors. Taken together, FZD3 facilitates VWFs viability, ECM degradation, and inhibits apoptosis via the Wnt pathway in POP. The findings provide a potential target for the treatment of POP.

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Single-cell transcriptomic data reveal the increase in extracellular matrix organization and antigen presentation abilities of fibroblasts and smooth muscle cells in patients with pelvic organ prolapse

Cited by 2 publications

References 22 publications

Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells

Functional outcome of the anterior vaginal wall in a pelvic surgery injury rat model after treatment with stem cell-derived progenitors of smooth muscle cells

FZD3 regulates the viability, apoptosis, and extracellular matrix degradation of vaginal wall fibroblasts in pelvic organ prolapse via the Wnt signaling pathway

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