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脂肪组织来源干细胞在子宫内膜异位症的临床前小鼠模型中的营养和免疫调节作用。

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

机构信息

Department of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

出版信息

Sci Rep. 2022 May 16;12(1):8031. doi: 10.1038/s41598-022-11891-5.

DOI:10.1038/s41598-022-11891-5
PMID:35577867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9110373/
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.

摘要

子宫内膜异位症表现出基质纤维化和异位上皮细胞增殖等神秘的病理特征,被认为是一种难治性疾病。间充质干细胞通过其营养和免疫调节特性来调节基质组织的纤维化。为了研究干细胞在治疗子宫内膜异位症中的潜力,我们检查了脂肪组织来源的干细胞(ASCs)给药后实验性子宫内膜异位症小鼠模型中子宫内膜异位症样病变的二次形态和分子改变。发现输注的 ASCs 整合在子宫内膜异位症样病变中。具有干细胞特性的 ASC 输注(早期传代 ASCs)伴随着基质纤维化的抑制和子宫内膜异位上皮细胞的增殖,抑制了子宫内膜异位症样病变的生长,并抑制了促炎和促纤维化细胞因子的表达,而没有干细胞特性的 ASC 输注(晚期传代 ASCs)则没有明显减轻子宫内膜异位症样病变。因此,ASCs 的营养和免疫调节特性可能调节子宫内膜异位症样病变中的纤维化,这表明通过积累临床前疗效的证据,再生医学可以被认为是子宫内膜异位症患者的一种创新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/cf9c25f08adc/41598_2022_11891_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/07a1b73059f3/41598_2022_11891_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/1e5f3a90baa5/41598_2022_11891_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/cbc23e953735/41598_2022_11891_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/cf9c25f08adc/41598_2022_11891_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/07a1b73059f3/41598_2022_11891_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/1e5f3a90baa5/41598_2022_11891_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/cbc23e953735/41598_2022_11891_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba25/9110373/cf9c25f08adc/41598_2022_11891_Fig4_HTML.jpg

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