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

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 ge...

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Published in:Biomaterials 2021-11, Vol.278, p.121156-121156, Article 121156
Main Authors: Choi, Da Hyeon, Lee, Kyeong Eun, Oh, Se-Young, Lee, Si Min, Jo, Beom Soo, Lee, Jue-Yeon, Park, Jong-Chul, Park, Yoon Jeong, Park, Ki Dong, Jo, Inho, Park, Yoon Shin
Format: Article
Language:English
Subjects:
Animals
Bone regeneration
Cell surface GRP78
Glucose
Glucose-regulated protein 78
Heat-Shock Proteins
Hydrogels
Membrane Proteins
Mesenchymal Stem Cells
Osteogenesis
Palatine Tonsil
Proteomics
Rats
Reactive Oxygen Species
ROS releasing hydrogel
Senescence
Tonsil-derived mesenchymal stem cells
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Summary: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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2021.121156