Gaafar Taghrid, Osman Omneya, Osman Amira, Attia Wael, Hamza Hala, El Hawary Rabab
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University [Stem Cell Research Unit, Pediatric Hospital, Cairo University], Kasr El Aini, Cairo, 11562, Egypt,
Mol Cell Biochem. 2014 Oct;395(1-2):29-43. doi: 10.1007/s11010-014-2109-0. Epub 2014 Jun 1.
Postulated Stem/progenitor cells involved in endometrium regeneration are epithelial, mesenchymal, and endothelial. Bone marrow (BM) has been implicated in endometrial stem cells. We aimed at studying gene expression profiling of endometrial mesenchymal stem cells compared to BM MSCS to better understand their nature and functional phenotype. Endometrial tissues were obtained from premenopausal hysterectomies (n = 3), minced and enzymatically digested as well as Normal BM aspirates (n=3). Immunophenotyping, differentiation to mesoderm, and proliferation were studied. The expression profile of 84 genes relevant to mesenchymal stem cells was performed. Fold change calculations were determined with SA Biosciences data analysis software. VEGF, G-CSF, and GM-CSF in cultures supernatants of MSCs were assayed by Luminex immunoassay. Endo MSCs possess properties similar to BM MSCs. Cumulative population doubling was significantly higher in Endo MSCs compared to BM MSCs (p < 0.001). 52 core genes were shared between both generated MSCs including stemness, self-renewal, members of the Notch, TGFB, FGF, and WNT.16 downregulated genes (VCAM, IGF1)and 16 upregulated in Endo MSCs compared to BM (p < 0.05 → fourfolds). They included mostly cytokine and growth factor genes G-CSF, GM-CSF, VWF, IL1b, GDF15, and KDR. VEGF and G-CSF levels were higher in Endo MSCs supernatants (p < 0.0001). Cells sharing MSC and endothelial cell characteristics could be isolated from the human endometrium. Endo MSCs share a core genetic profile with BM MSCs including stemness. They show upregulation of genes involved in vasculogenesis, angiogenesis, cell adhesion, growth proliferation, migration, and differentiation of endothelial cells, all contributing to endometrial function.
推测参与子宫内膜再生的干/祖细胞有上皮细胞、间充质细胞和内皮细胞。骨髓已被认为与子宫内膜干细胞有关。我们旨在研究与骨髓间充质干细胞相比，子宫内膜间充质干细胞的基因表达谱，以更好地了解它们的性质和功能表型。从绝经前子宫切除术患者（n = 3）获取子宫内膜组织，切碎并进行酶消化，同时获取正常骨髓抽吸物（n = 3）。对其进行免疫表型分析、向中胚层的分化以及增殖研究。检测了与间充质干细胞相关的84个基因的表达谱。使用SA生物科学数据分析软件进行倍数变化计算。通过Luminex免疫测定法检测间充质干细胞培养上清液中的VEGF、G-CSF和GM-CSF。子宫内膜间充质干细胞具有与骨髓间充质干细胞相似的特性。与骨髓间充质干细胞相比，子宫内膜间充质干细胞的累积群体倍增显著更高（p < 0.001）。两种生成的间充质干细胞共有52个核心基因，包括干性、自我更新、Notch、TGFB、FGF和WNT的成员。与骨髓相比，子宫内膜间充质干细胞中有16个基因下调（VCAM、IGF1），16个基因上调（p < 0.05 → 四倍）。它们主要包括细胞因子和生长因子基因G-CSF、GM-CSF、VWF、IL1b、GDF15和KDR。子宫内膜间充质干细胞上清液中的VEGF和G-CSF水平更高（p < 0.0001）。可以从人子宫内膜中分离出兼具间充质干细胞和内皮细胞特征的细胞。子宫内膜间充质干细胞与骨髓间充质干细胞共享包括干性在内的核心基因谱。它们显示出参与血管生成、血管新生、细胞黏附、生长增殖、迁移以及内皮细胞分化的基因上调，所有这些都有助于子宫内膜的功能。
