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Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78

Authors
 Da Hyeon Choi  ;  Kyeong Eun Lee  ;  Se-Young Oh  ;  Si Min Lee  ;  Beom Soo Jo  ;  Jue-Yeon Lee  ;  Jong-Chul Park  ;  Yoon Jeong Park  ;  Ki Dong Park  ;  Inho Jo  ;  Yoon Shin Park 
Citation
 BIOMATERIALS, Vol.278 : 121156, 2021-11 
Journal Title
BIOMATERIALS
ISSN
 0142-9612 
Issue Date
2021-11
MeSH
Animals ; Glucose ; Heat-Shock Proteins* ; Hydrogels ; Membrane Proteins ; Mesenchymal Stem Cells* ; Osteogenesis ; Palatine Tonsil ; Proteomics ; Rats ; Reactive Oxygen Species*
Keywords
Bone regeneration ; Cell surface GRP78+ ; Glucose-regulated protein 78 ; ROS releasing hydrogel ; Senescence ; Tonsil-derived mesenchymal stem cells
Abstract
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.
Files in This Item:
T202125614.pdf Download
DOI
10.1016/j.biomaterials.2021.121156
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Park, Jong Chul(박종철) ORCID logo https://orcid.org/0000-0003-0083-5991
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188142
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