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Tracking of human embryonic stem cell-derived mesenchymal stem cells in premature ovarian failure model mice
Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2021-08-26 , DOI: 10.1016/j.bbrc.2021.08.063
Khadijeh Bahrehbar 1 , Mostafa Khanjarpoor Malakhond 2 , Sedigheh Gholami 3
Affiliation  

Premature ovarian failure (POF) is defined by amenorrhea, hypoestrogenism, elevated gonadotropin levels, and infertility. Chemotherapeutic agents are the most gonadotoxic agents that lead to POF. Although some previous studies have presented that mesenchymal stem cells (MSCs) transplantation could rescue the ovary function of POF animal models through the paracrine pathway, these mechanisms require further investigation. However, mechanisms of embryonic stem cell-derived MSCs (ES-MSCs) therapeutic effects on POF animal models have not been fully investigated yet. This study aimed to evaluate the migration and distribution of ES-MSCs in a model of chemotherapy-induced POF.

Female mice received intraperitoneal injections of cyclophosphamide (Cy) to induce POF. Then, MSCs were labeled with green fluorescent protein (GFP) in vitro and injected intravenously into POF mice, and the distribution of MSCs was dynamically monitored at 1 week after transplantation. We harvested the lungs, liver, spleen, ovaries, heart, and kidneys 1 week after transplantation. The sections of these tissues were observed under the fluorescent microscope.

More than 70% MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including lungs, liver, spleen, ovaries, heart, and kidneys of POF mice. In mice, at 1week after intravenous transplantation, GFP labeled ES-MSCs were observed in the lungs, liver, spleen, ovaries, heart, and kidneys of POF mice, and the number of GFP labeled ES-MSCs in lungs, ovaries, and heart were higher than that in the spleen, kidneys, and liver. Our results revealed intravenously implanted ES-MSCs could migrate into the various tissues in chemotherapy-induced damaged POF mice.



中文翻译:


卵巢早衰模型小鼠中人胚胎干细胞来源的间充质干细胞的追踪



卵巢早衰(POF)的定义是闭经、雌激素不足、促性腺激素水平升高和不孕。化疗药物是导致 POF 性腺毒性最强的药物。尽管之前的一些研究表明间充质干细胞(MSC)移植可以通过旁分泌途径挽救POF动物模型的卵巢功能,但这些机制需要进一步研究。然而,胚胎干细胞源性间充质干细胞(ES-MSCs)对 POF 动物模型的治疗作用机制尚未得到充分研究。本研究旨在评估化疗诱导 POF 模型中 ES-MSC 的迁移和分布。


雌性小鼠腹腔注射环磷酰胺(Cy)以诱导 POF。然后,在体外用绿色荧光蛋白(GFP)标记MSC,静脉注射给POF小鼠,移植后1周动态监测MSC的分布。移植后 1 周,我们收获了肺、肝、脾、卵巢、心脏和肾。在荧光显微镜下观察这些组织的切片。


标记后72小时,超过70%的MSC成功被GFP标记。 MSCs均匀分布于POF小鼠的肺、肝、脾、卵巢、心脏、肾等多个器官和组织中。小鼠静脉移植后1周,在POF小鼠的肺、肝、脾、卵巢、心脏、肾中观察到GFP标记的ES-MSCs,以及肺、卵巢、心脏中GFP标记的ES-MSCs的数量高于脾、肾、肝。我们的结果显示,静脉内植入的 ES-MSC 可以迁移到化疗引起的 POF 小鼠损伤的各种组织中。

更新日期:2021-09-03
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