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KMID : 1377020210180020253
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Tissue Engineering and Regenerative Medicine
2021 Volume.18 No. 2 p.253 ~ p.264
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A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells
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Kim Hee-Yeon
Lee Young-Hay
Yoon Hee-Soo
Kim Yu-Hee
Cho Kyong-A
Woo So-Youn
Kim Han-Su
Park Bo-Young
Jung Sung-Chul
Jo In-Ho
Park Woo-Jae
Park Joo-Won
Ryu Kyung-Ha
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Abstract
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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 17β-estradiol secretion upon testosterone addition. Furthermore, CYP11A1, CYP17A1, and 3β-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.
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KEYWORD
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Estrogen, Tonsil, Mesenchymal stem cell, Secretion, Cytochrome P450 family 19 subfamily A member 1
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