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 Park7, Kyung-Ha Ryu8. 1. Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea. 2. Department of Microbiology, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea. 3. Department of Otolaryngology, College of Medicine, Ewha Womans University, Seoul, 07985, South Korea. 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. 6. Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, South Korea. 7. Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea. joowon.park@ewha.ac.kr. 8. Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea. ykh@ewha.ac.kr.
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 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.
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.
Entities:
Keywords:
Cytochrome P450 family 19 subfamily A member 1; Estrogen; Mesenchymal stem cell; Secretion; Tonsil
Authors: Ron B Mitchell; Sanford M Archer; Stacey L Ishman; Richard M Rosenfeld; Sarah Coles; Sandra A Finestone; Norman R Friedman; Terri Giordano; Douglas M Hildrew; Tae W Kim; Robin M Lloyd; Sanjay R Parikh; Stanford T Shulman; David L Walner; Sandra A Walsh; Lorraine C Nnacheta Journal: Otolaryngol Head Neck Surg Date: 2019-02 Impact factor: 3.497
Authors: Florian Wagenlehner; Undraga Schagdarsurengin; Nils Nesheim; Stuart Ellem; Temuujin Dansranjavin; Christina Hagenkötter; Elena Berg; Rupert Schambeck; Hans-Christian Schuppe; Adrian Pilatz; Gail Risbridger; Wolfgang Weidner Journal: Oncotarget Date: 2018-04-13