Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells
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 parathyroide...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/2/715 |
| _version_ | 1797493362224267264 |
|---|---|
| author | Ji Yeon Kim Saeyoung Park Se-Young Oh Yu Hwa Nam Young Min Choi Yeonzi Choi Ha Yeong Kim Soo Yeon Jung Han Su Kim Inho Jo Sung-Chul Jung |
| author_facet | Ji Yeon Kim Saeyoung Park Se-Young Oh Yu Hwa Nam Young Min Choi Yeonzi Choi Ha Yeong Kim Soo Yeon Jung Han Su Kim Inho Jo Sung-Chul Jung |
| author_sort | Ji Yeon Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:18:56Z |
| format | Article |
| id | doaj.art-59ddaa9e936340e2b12591702e80864b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:18:56Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-59ddaa9e936340e2b12591702e80864b2023-11-23T14:03:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123271510.3390/ijms23020715Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing CellsJi Yeon Kim0Saeyoung Park1Se-Young Oh2Yu Hwa Nam3Young Min Choi4Yeonzi Choi5Ha Yeong Kim6Soo Yeon Jung7Han Su Kim8Inho Jo9Sung-Chul Jung10Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartments of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartments of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartments of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartments of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartments of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartments of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, KoreaMesenchymal 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.https://www.mdpi.com/1422-0067/23/2/715tonsil-derived mesenchymal stem cellsparathyroid-hormone-releasing cellsdifferentiationcontact inhibitiondonor-dependent variation |
| spellingShingle | Ji Yeon Kim Saeyoung Park Se-Young Oh Yu Hwa Nam Young Min Choi Yeonzi Choi Ha Yeong Kim Soo Yeon Jung Han Su Kim Inho Jo Sung-Chul Jung Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells International Journal of Molecular Sciences tonsil-derived mesenchymal stem cells parathyroid-hormone-releasing cells differentiation contact inhibition donor-dependent variation |
| title | Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells |
| title_full | Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells |
| title_fullStr | Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells |
| title_full_unstemmed | Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells |
| title_short | Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells |
| title_sort | density dependent differentiation of tonsil derived mesenchymal stem cells into parathyroid hormone releasing cells |
| topic | tonsil-derived mesenchymal stem cells parathyroid-hormone-releasing cells differentiation contact inhibition donor-dependent variation |
| url | https://www.mdpi.com/1422-0067/23/2/715 |
| work_keys_str_mv | AT jiyeonkim densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT saeyoungpark densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT seyoungoh densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT yuhwanam densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT youngminchoi densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT yeonzichoi densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT hayeongkim densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT sooyeonjung densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT hansukim densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT inhojo densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells AT sungchuljung densitydependentdifferentiationoftonsilderivedmesenchymalstemcellsintoparathyroidhormonereleasingcells |