Tissue Eng Regen Med.
2017 Aug;14(4):411-420. 10.1007/s13770-017-0042-5.
Intracellular Remodeling and Accumulation of Aberrant Lysosomes in Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Like Cells
- Affiliations
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- 1Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
- 2Department of Molecular Medicine, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea.
- 3Ewha Tonsil-Derived Mesenchymal Stem Cells Research Center (ETSRC), School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea.
- 4Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea. sevent@ewha.ac.kr
- 5Major in Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk 28644, Republic of Korea. pys@cbnu.ac.kr
- KMID: 2394975
- DOI: http://doi.org/10.1007/s13770-017-0042-5
Abstract
- Differentiation of mesenchymal stem cells (MSC) into a variety of cell lineages such as adipocytes, osteocytes, and chondrocytes is often accompanied up-regulation of autophagy. In our study, we demonstrated that the expression of autophagy-associated proteins (p-Beclin 1, LC3A, LC3B, p-AMPK, p-mTOR and ATG3, ATG7, and ATG12-5) over a period of time was hardly distinguishable from control tonsil-derived MSC (TMSC). Despite the unnoticeable difference in autophagy activation between differentiated TMSC (dTMSC) and the control (cTMSC), we reported significant changes in intracellular compositions in differentiated TMSC into functional parathyroid-like cells secreting parathyroid hormone (PTH). By using transmission electron microscopy (TEM), we observed accumulation of multivesicular bodies (MVB) comprising small, degraded compartments densely accumulated as dark granular or amorphous clumps, multilamellar bodies and lipid droplets in dTMSC. However, no such structures were found in cTMSC. These results suggest that differentiation of TMSC into parathyroid-like cells producing PTH hormone is hardly dependent on autophagy activation in the beginning of our conditions. Furthermore, our results of intracellular remodeling and accumulated endo-lysosomal storage bodies in the later stages of TMSC differentiation present a possible role of the structures in PTH secretion.
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