Tissue Eng Regen Med.  2021 Apr;18(2):253-264. 10.1007/s13770-020-00307-y.

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

Affiliations
  • 1Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
  • 2Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
  • 3Department of Otolaryngology, College of Medicine, Ewha Womans University, Seoul 07985, South Korea
  • 4Department of Plastic and Reconstructive Surgery, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
  • 5Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, South Korea
  • 6Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, South Korea
  • 7Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul 07804, South Korea

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.

Keyword

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