Hajazimian Saba, Maleki Masoud, Mehrabad Shahla Danaei, Isazadeh Alireza
Department of Genetics, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Gynecology Department, Eastern Azerbaijan ACECR ART Center, Eastern Azerbaijan Branch of ACECR, Tabriz, Iran.
Reproduction. 2020 May;159(5):549-558. doi: 10.1530/REP-19-0597.
Endometriosis is a relatively benign disease characterized by endometrial tumors and uterus stroma. Apoptosis suppression is one of the most important pathological processes of endometriosis. Recently, several studies reported that human Wharton's jelly stem cells (hWJSCs) can inhibit growth and proliferation of various cancer cells through induction of apoptosis. Therefore, the aim of the present study was to investigate the effects of hWJSCs conditioned medium (hWJSC-CM) and cell-free lysate (hWJSC-CL) on endometriosis cells in vitro. In the present study, effects of different concentrations of hWJSC-CM and hWJSC-CL on viability and proliferation, morphological alterations, colony formation, migration, invasion, and apoptosis of endometriosis cells were evaluated. Our results showed that hWJSC-CM and hWJSC-CL decrease viability and proliferation, colony formation, migration, and invasion, as well as increase morphological alterations and apoptosis of endometriosis cells, in a concentration- and time-dependent manner. Decreased migration and invasion of treated endometriosis cells with hWJSC-CM and hWJSC-CL may be due to decrease of MMP-2 and MMP-9 gene expression. Moreover, induction of apoptosis in treated endometriosis cells can be due to regulation of apoptosis-related genes expression, including BAX, BCL-2, SMAC, and SURVIVIN. The results of the present study suggest that hWJSC-CM and hWJSC-CL can inhibit endometriosis cells at a mild-to-moderate level through various physiological mechanisms. However, further studies on animal models are necessary to achieve more accurate results.
子宫内膜异位症是一种相对良性的疾病,其特征为子宫内膜肿瘤和子宫基质。细胞凋亡抑制是子宫内膜异位症最重要的病理过程之一。最近,多项研究报道人脐带华通氏胶间充质干细胞(hWJSCs)可通过诱导细胞凋亡来抑制多种癌细胞的生长和增殖。因此,本研究旨在探讨hWJSCs条件培养基(hWJSC-CM)和无细胞裂解液(hWJSC-CL)对体外子宫内膜异位症细胞的影响。在本研究中,评估了不同浓度的hWJSC-CM和hWJSC-CL对子宫内膜异位症细胞活力、增殖、形态改变、集落形成、迁移、侵袭及凋亡的影响。我们的结果表明,hWJSC-CM和hWJSC-CL以浓度和时间依赖性方式降低子宫内膜异位症细胞的活力、增殖、集落形成、迁移和侵袭,同时增加其形态改变和凋亡。hWJSC-CM和hWJSC-CL处理的子宫内膜异位症细胞迁移和侵袭能力降低可能是由于MMP-2和MMP-9基因表达下降所致。此外,hWJSC-CM和hWJSC-CL处理的子宫内膜异位症细胞凋亡诱导可能归因于凋亡相关基因表达的调控,包括BAX、BCL-2、SMAC和SURVIVIN。本研究结果表明,hWJSC-CM和hWJSC-CL可通过多种生理机制在轻度至中度水平抑制子宫内膜异位症细胞。然而,需要对动物模型进行进一步研究以获得更准确的结果。