A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells

Hee Yeon Kim, Younghay Lee, Hee Soo Yoon, Yu Hee Kim, Kyong A. Cho, So Youn Woo, Han Sun Kim, Bo Young Park, Sung Chul Jung, Inho Jo, Woo Jae Park, Joo Won Park, Kyung Ha Ryu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish
Pages (from-to)253-264
Number of pages12
JournalTissue Engineering and Regenerative Medicine
Issue number2
StatePublished - Apr 2021

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea grants funded by the Korean Government (Ministry of Education, Science and Technology) [NRF-2017R1E1A1A01073021] and by grants from the Health Technology R&D Project (HI18C2392) of the Ministry of Health and Welfare, Republic of Korea.

Publisher Copyright:
© 2020, The Korean Tissue Engineering and Regenerative Medicine Society.


  • Cytochrome P450 family 19 subfamily A member 1
  • Estrogen
  • Mesenchymal stem cell
  • Secretion
  • Tonsil


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