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包裹在藻酸盐/明胶水凝胶中的子宫内膜干细胞治疗多囊卵巢综合征的潜力

Therapeutic potential of endometrial stem cells encapsulated in alginate/gelatin hydrogel to treat of polycystic ovary syndrome.

作者信息

Kouchakzadeh Fatemeh, Ebrahimi-Barough Somayeh, Aflatoonian Behrouz, Ai Jafar, Mazaheri Fahime, Montazeri Fateme, Hajizadeh-Tafti Fatemeh, Golzadeh Jalal, Naser Reza, Sepehri Masoumeh, Kalantar Seyed Mehdi

机构信息

Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

出版信息

Regen Ther. 2024 Aug 30;26:693-707. doi: 10.1016/j.reth.2024.08.016. eCollection 2024 Jun.

Abstract

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often leading to infertility due to anovulation. Recent advances suggest that endometrial stem cells (EnSCs) hold considerable promise for tissue regeneration, which could be pivotal in treating PCOS. To enhance the survival and stabilization of EnSCs within the ovary, the EnSCs were encapsulated in an injectable alginate/gelatin hydrogel (SC-H), which has excellent biocompatibility to support the survival of EnSCs. Polycystic ovary syndrome was induced in female Wistar rats using intraperitoneal injection of letrozole over 21 days. Then the rats were treated with SC, SC-H and clomiphene citrate for one-month post-PCOS induction. The effects of these treatments were evaluated based on changes in body and ovarian weights, inflammatory markers, endocrine profiles, and ovarian histology. The Induction of PCOS led to a significant increase in body and ovarian cyst weight, elevated serum levels of testosterone, luteinizing hormone (LH), and anti-Müllerian hormone (AMH), alongside reduced follicle-stimulating hormone (FSH) and progesterone levels. Histologically, there was a decrease in granulosa cells, immature follicles, and corpus luteum numbers. Treatment with SC and SC-H significantly mitigated these alterations, indicating improved PCOS conditions. Our findings demonstrate that SC and SC-H treatments can effectively ameliorate the symptoms of letrozole-induced PCOS in rats, primarily through their anti-inflammatory effects. This study lays the groundwork for potential clinical applications of EnSCs encapsulated in alginate/gelatin hydrogel as a novel therapeutic strategy for PCOS, highlighting the importance of biomaterials in stem cell-based therapies.

摘要

多囊卵巢综合征(PCOS)是一种常见的女性内分泌紊乱疾病,常因无排卵导致不孕。最近的研究进展表明,子宫内膜干细胞(EnSCs)在组织再生方面具有巨大潜力,这可能是治疗PCOS的关键。为了提高EnSCs在卵巢内的存活率和稳定性,将EnSCs封装在可注射的海藻酸盐/明胶水凝胶(SC-H)中,该水凝胶具有优异的生物相容性以支持EnSCs的存活。通过腹腔注射来曲唑21天诱导雌性Wistar大鼠患多囊卵巢综合征。然后在诱导PCOS后对大鼠进行SC、SC-H和枸橼酸氯米芬治疗1个月。根据体重和卵巢重量的变化、炎症标志物、内分泌谱以及卵巢组织学来评估这些治疗的效果。PCOS的诱导导致体重和卵巢囊肿重量显著增加,血清睾酮、黄体生成素(LH)和抗苗勒管激素(AMH)水平升高,同时促卵泡生成素(FSH)和孕酮水平降低。组织学上,颗粒细胞、未成熟卵泡和黄体数量减少。SC和SC-H治疗显著减轻了这些改变,表明PCOS状况有所改善。我们的研究结果表明,SC和SC-H治疗可以有效改善来曲唑诱导的大鼠PCOS症状,主要是通过它们的抗炎作用。本研究为将海藻酸盐/明胶水凝胶封装的EnSCs作为PCOS的一种新型治疗策略的潜在临床应用奠定了基础,突出了生物材料在基于干细胞的治疗中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/363c/11403143/f34afdd29c2f/gr1.jpg

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