Intracellular Remodeling and Accumulation of Aberrant Lysosomes in Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Like Cells.
10.1007/s13770-017-0042-5
- Author:
Young Il JO
1
;
Gyungah KIM
;
Yoon Mi JIN
;
Yoon Jeong PARK
;
Han Su KIM
;
Yoon Shin PARK
Author Information
1. Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Tonsil-derived mesenchymal stem cells;
Autophagy;
Parathyroid-like differentiation;
Multivesicular bodies;
Multilamellar bodies
- MeSH:
Adipocytes;
Autophagy;
Cell Lineage;
Chondrocytes;
Lipid Droplets;
Lysosomes*;
Mesenchymal Stromal Cells*;
Microscopy, Electron, Transmission;
Multivesicular Bodies;
Osteocytes;
Parathyroid Hormone;
Up-Regulation
- From:
Tissue Engineering and Regenerative Medicine
2017;14(4):411-420
- CountryRepublic of Korea
- Language:English
-
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.
