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3D-cultured human placenta-derived mesenchymal stem cell spheroids enhance ovary function by inducing folliculogenesis.
Scientific Reports ( IF 4.6 ) Pub Date : 2018-Oct-17 , DOI: 10.1038/s41598-018-33575-9
Tae-Hee Kim , Jong Ho Choi , Yesl Jun , Seung Mook Lim , Sohae Park , Jin-Young Paek , Sang-Hoon Lee , Ji-Young Hwang , Gi Jin Kim

Placenta-derived mesenchymal stem cells (PD-MSCs) have numerous advantages over other adult MSCs that make them an attractive cell source for regenerative medicine. Here, we demonstrate the therapeutic effect of PD-MSCs in ovariectomized (Ovx) rats and compare their efficacy when generated via a conventional monolayer culture system (2D, naïve) and a spheroid culture system (3D, spheroid). PD-MSC transplantation significantly increased the estradiol level in Ovx rats compared with the non-transplantation (NTx) group. In particular, the estradiol level in the Spheroid group was significantly higher than that in the Naïve group at 2 weeks. Spheroid PD-MSCs exhibited a significantly higher efficiency of engraftment onto ovarian tissues at 2 weeks. The mRNA and protein expression levels of Nanos3, Nobox, and Lhx8 were also significantly increased in the Spheroid group compared with those in the NTx group at 1 and 2 weeks. These results suggest that PD-MSC transplantation can restore ovarian function in Ovx rats by increasing estrogen production and enhancing folliculogenesis-related gene expression levels and further indicate that spheroid-cultured PD-MSCs have enhanced therapeutic potential via increased engraftment efficiency. These findings improve our understanding of stem-cell-based therapies for reproductive systems and may suggest new avenues for developing efficient therapies using 3D cultivation systems.

中文翻译:

3D培养的人胎盘来源的间充质干细胞球体通过诱导卵泡生成来增强卵巢功能。

胎盘来源的间充质干细胞(PD-MSC)与其他成年MSC相比具有许多优势,这使它们成为再生医学的有吸引力的细胞来源。在这里,我们展示了PD-MSC在卵巢切除(Ovx)大鼠中的治疗效果,并比较了通过常规单层培养系统(2D,纯朴)和球体培养系统(3D,球体)产生的PD-MSC的疗效。与非移植(NTx)组相比,PD-MSC移植可显着提高Ovx大鼠的雌二醇水平。特别是在2周时,Spheroid组的雌二醇水平显着高于Naive组。球形PD-MSC在第2周显示出明显更高的卵巢组织移植效率。Nanos3,Nobox,在第1周和第2周,与NTx组相比,Spheroid组中的Lhx8和Lhx8也显着增加。这些结果表明,PD-MSC移植可以通过增加雌激素的产生并提高卵泡生成相关基因的表达水平来恢复Ovx大鼠的卵巢功能,并且进一步表明,通过球体培养的PD-MSC可以通过提高植入效率来增强治疗潜力。这些发现提高了我们对生殖系统干细胞疗法的理解,并可能为使用3D种植系统开发有效疗法提供了新途径。这些结果表明,PD-MSC移植可以通过增加雌激素的产生并提高卵泡生成相关基因的表达水平来恢复Ovx大鼠的卵巢功能,并且进一步表明,通过球体培养的PD-MSC可以通过提高植入效率来增强治疗潜力。这些发现提高了我们对生殖系统干细胞疗法的理解,并可能为使用3D种植系统开发有效疗法提供了新途径。这些结果表明,PD-MSC移植可以通过增加雌激素的产生并提高卵泡生成相关基因的表达水平来恢复Ovx大鼠的卵巢功能,并且进一步表明,通过球体培养的PD-MSC可以通过提高植入效率来增强治疗潜力。这些发现提高了我们对生殖系统干细胞疗法的理解,并可能为使用3D种植系统开发有效疗法提供了新途径。
更新日期:2018-10-17
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