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Trophic and immunomodulatory effects of adipose tissue derived stem cells in a preclinical murine model of endometriosis.

ABSTRACT: Endometriosis, which exhibits enigmatic pathological features such as stromal fibrosis and proliferation of ectopic epithelial cells, is known as a refractory disease. Mesenchymal stem cells modulate the fibrosis in stromal tissues through their trophic and immunomodulatory properties. To investigate the potential of stem cells in treating endometriosis, we examined the secondary morphology and molecular alterations in endometriosis-like lesions after the administration of adipose tissue-derived stem cells (ASCs) to an experimental murine model of endometriosis. The infused ASCs were found integrated in the endometriosis-like lesions. Accompanied by the suppression of stromal fibrosis and proliferation of endometriotic epithelial cells, the infusion of ASCs with stemness potential (early passage of ASCs) suppressed the growth of endometriosis-like lesions and inhibited the expression of pro-inflammatory and pro-fibrotic cytokines, whereas no significant attenuation of endometriosis-like lesions occurred after the infusion of ASCs without stemness potential (late passage of ASCs). Accordingly, the trophic and immunomodulatory properties of ASCs may regulate fibrosis in endometriosis-like lesions, suggesting that regenerative medicine could be recognized as an innovative treatment for patients with endometriosis through the accumulation of evidence of preclinical efficacy.

SUBMITTER: Hirakawa T

PROVIDER: S-EPMC9110373 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Trophic and immunomodulatory effects of adipose tissue derived stem cells in a preclinical murine model of endometriosis.

Hirakawa Toyofumi T Yotsumoto Fusanori F Shirasu Naoto N Kiyoshima Chihiro C Urushiyama Daichi D Yoshikawa Kenichi K Miyata Kohei K Kurakazu Masamitsu M Koga Kaori Azuma KA Aoki Mikiko M Nabeshima Kazuki K Koga Kaori S KS Osuga Yutaka Y Komatsu Hiroaki H Taniguchi Fuminori F Harada Tasuku T Yasunaga Shin'ichiro S Miyamoto Shingo S

Scientific reports 20220516 1

Endometriosis, which exhibits enigmatic pathological features such as stromal fibrosis and proliferation of ectopic epithelial cells, is known as a refractory disease. Mesenchymal stem cells modulate the fibrosis in stromal tissues through their trophic and immunomodulatory properties. To investigate the potential of stem cells in treating endometriosis, we examined the secondary morphology and molecular alterations in endometriosis-like lesions after the administration of adipose tissue-derived ...[more]

PMID: 35577867

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Project description:BackgroundAdipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapy due to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Unlike the subcutaneous abdominal fat depot, breast ASCs features are still not well recognized, limiting their possible therapeutic use. ASCs were found to exert immunomodulatory and antioxidative activities for maintaining homeostasis and functionality of diseased/damaged tissues. This study aims to investigate the immunomodulatory and antioxidative potentials of breast versus abdominal isolated ASCs to find out which anatomical site provides ASCs with better immunoregulatory and oxidative stress resistance capabilities.MethodsASCs were isolated from abdominal and breast tissues. Gene expression analysis was conducted for a panel of immunomodulatory and antioxidative genes, as well as adipokines and proliferation genes. Flow cytometric analysis of a group of immunomodulatory surface proteins was also performed. Finally, the significantly expressed genes have undergone protein-protein interaction and functional enrichment in silico analyses.ResultsOur results revealed similar morphological and phenotypic characteristics for both breast and abdominal ASCs. However, a significant elevation in the expression of two potent immunosuppressive genes, IL-10 and IDO as well as the expression of the multifaceted immunomodulatory adipokine, visfatin, was detected in breast versus abdominal ASCs. Moreover, a significant overexpression of the antioxidative genes, GPX1, SIRT5, and STAT3 and the proliferation marker, Ki67, was also observed in breast ASCs relative to abdominal ones. In silico analysis showed that both of the differentially upregulated immunomodulatory and antioxidative mediators integratively involved in multiple biological processes and pathways indicating their functional association.ConclusionBreast ASCs possess superior immunomodulatory and antioxidative capabilities over abdominal ASCs. Our findings shed light on the possible therapeutic applications of breast ASCs in immune-related and oxidative stress-associated diseases.

Dataset Information

Trophic and immunomodulatory effects of adipose tissue derived stem cells in a preclinical murine model of endometriosis.

Publications

Trophic and immunomodulatory effects of adipose tissue derived stem cells in a preclinical murine model of endometriosis.

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