A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells
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Online ISSN 2212-5469
ORIGINAL ARTICLE
A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells Hee-Yeon Kim1 • Younghay Lee1 • Hee-Soo Yoon1 • Yu-Hee Kim2 • Kyong-A Cho2 • So-Youn Woo2 • Han Sun Kim3 • Bo-Young Park4 • Sung-Chul Jung1 • Inho Jo5 • Woo-Jae Park6 • Joo-Won Park1 • Kyung-Ha Ryu7
Received: 29 August 2020 / Revised: 24 September 2020 / Accepted: 29 September 2020 Ó The Korean Tissue Engineering and Regenerative Medicine Society 2020
Abstract BACKGROUND: The advantages of tonsil-derived mesenchymal stem cells (TMSCs) over other mesenchymal stem cells (MSCs) include higher proliferation rates, various differentiation potentials, efficient immune-modulating capacity, and ease of obtainment. Specifically, TMSCs have been shown to differentiate into the endodermal lineage. Estrogen deficiency is a major cause of postmenopausal osteoporosis and is associated with higher incidences of ischemic heart disease and cerebrovascular attacks during the postmenopausal period. Therefore, stem cell-derived, estrogen-secreting cells might be used for estrogen deficiency. METHODS: Here, we developed a novel method that utilizes retinoic acid, insulin-like growth factor-1, basic fibroblast growth factor, and dexamethasone to evaluate the differentiating potential of TMSCs into estrogen-secreting cells. The efficacy of the novel differentiating method for generation of estrogen-secreting cells was also evaluated with bone marrow- and adipose tissue-derived MSCs. RESULTS: Incubating TMSCs in differentiating media induced the gene expression of cytochrome P450 19A1 (CYP19A1), which plays a key role in estrogen biosynthesis, and increased 17b-estradiol secretion upon testosterone addition. Furthermore, CYP11A1, CYP17A1, and 3b-hydroxysteroid dehydrogenase type-1 gene expression levels were significantly increased in TMSCs. In bone marrow-derived and adipose tissue-derived MSCs, this differentiation method also induced the gene expression of CYP19A1, but not CYP17A1, suggesting TMSCs are a superior source for estrogen secretion. CONCLUSION: These results imply that TMSCs can differentiate into functional estrogen-secreting cells, thus providing a novel, alternative cell therapy for estrogen deficiency. Keywords Estrogen Tonsil Mesenchymal stem cell Secretion Cytochrome P450 family 19 subfamily A member 1
Hee-Yeon Kim and Younghay Lee have contributed equally to this work. 4
Department of Plastic and Reconstructive Surgery, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
5
Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
6
Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, South Korea
Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
7
Department of Pediatrics, College of Medicine, Ewha Womans University,
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