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Sci Rep. 2018 Oct 17;8(1):15313. doi: 10.1038/s41598-018-33575-9.

3D-cultured human placenta-derived mesenchymal stem cell spheroids enhance ovary function by inducing folliculogenesis.

Author information

1
Department of Obstetrics and Gynecology, Soonchunhyang University College of Medicine Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon-si, Gyunggi-do, Republic of Korea.
2
Department of Biomedical Science, CHA University, 689, Sampyeong-dong, Bundang-gu, Seongnam-si, Gyunggi-do, Republic of Korea.
3
KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, Republic of Korea.
4
Department of Clinical Pathology, CHA Gangnam Medical Center, CHA University, School of Medicine, 566 Nonhyun-ro, Gangnam-gu, Seoul, Republic of Korea.
5
Department of Biomedical Engineering, College of Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, Republic of Korea.
6
Department of Biomedical Engineering, College of Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, Republic of Korea. jyhwang@korea.ac.kr.
7
Department of Biomedical Science, CHA University, 689, Sampyeong-dong, Bundang-gu, Seongnam-si, Gyunggi-do, Republic of Korea. gjkim@cha.ac.kr.

Abstract

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.

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