Controlling the senescence of mesenchymal stem cells (MSCs) is essential for improving the efficacy of MSC-based therapies. Here, a model of MSC senescence was established by replicative subculture in tonsil-derived MSCs (TMSCs) using senescence-associated β-galactosidase, telomere-length related genes, stemness, and mitochondrial metabolism. Using transcriptomic and proteomic analyses, we identified glucose-regulated protein 78 (GRP78) as a unique MSC senescence marker. With increasing cell passage number, GRP78 gradually translocated from the cell surface and cytosol to the (peri)nuclear region of TMSCs. A gelatin-based hydrogel releasing a sustained, low level of reactive oxygen species (ROS-hydrogel) was used to improve TMSC quiescence and self-renewal. TMSCs expressing cell surface-specific GRP78 (csGRP78+), collected by magnetic sorting, showed better stem cell function and higher mitochondrial metabolism than unsorted cells. Implantation of csGRP78+ cells embedded in ROS-hydrogel in rats with calvarial defects resulted in increased bone regeneration. Thus, csGRP78 is a promising biomarker of senescent TMSCs, and the combined use of csGRP78+ cells and ROS-hydrogel improved the regenerative capacity of TMSCs by regulating GRP78 translocation.
|Publication status||Published - 2021 Nov|
Bibliographical noteFunding Information:
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea ( NRF ) funded by the Ministry of Science, ICT & Future Planning (No. 2017M3A9B3063635 , 2017M3A9B3063636 , 2019M3A9H1032376 , and 2020R1A2C1101340 ) and from Priority Research Centers Program (No. 2019R1A6A1A11051471 ).
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Mechanics of Materials