Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells
- 주제(키워드) tonsil-derived mesenchymal stem cells , parathyroid-hormone-releasing cells , differentiation , contact inhibition , donor-dependent variation
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Chemistry, Multidisciplinary
- 설명문(일반) [Kim, Ji Yeon; Park, Saeyoung; Nam, Yu Hwa; Choi, Yeonzi; Jung, Sung-Chul] Ewha Womans Univ, Coll Med, Dept Biochem, Seoul 07804, South Korea; [Oh, Se-Young; Choi, Young Min; Jo, Inho] Ewha Womans Univ, Coll Med, Dept Mol Med, Seoul 07804, South Korea; [Nam, Yu Hwa; Choi, Young Min; Choi, Yeonzi; Jo, Inho; Jung, Sung-Chul] Ewha Womans Univ, Grad Program Syst Hlth Sci & Engn, Seoul 07804, South Korea; [Kim, Ha Yeong; Jung, Soo Yeon; Kim, Han Su] Ewha Womans Univ, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Seoul 07804, South Korea; [Kim, Ji Yeon] Asan Med Ctr, Dept Convergence Med, Seoul 05505, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190802
- 본문언어 영어
- Published As https://doi.org/10.3390/ijms23020715
- PubMed https://pubmed.ncbi.nlm.nih.gov/35054901
초록/요약
Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.
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