한빛사논문
Da Hyeon Choia,1, Kyeong Eun Leea,1, Se-Young Ohb,c, Si Min Leed, Beom Soo Joe,f, Jue-Yeon Leef, Jong-Chul Parkg, Yoon Jeong Parke,f,*, Ki Dong Parkd,*, Inho Job,c,*, Yoon Shin Parka,*
aDepartment of Biological Sciences and Biotechnology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, 28644, Republic of Korea bDepartment of Molecular Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea cGraduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul, 07804, Republic of Korea dDepartment of Molecular Science and Technology, Ajou University, 5 Woncheon, Yeongtong, Suwon, 16499, Republic of Korea eDepartment of Dental Regenerative Bioengineering and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea fCentral Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea gCellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
1These authors contributed equally to this work.
*Corresponding author.
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.
Keywords : Cell surface GRP78+, Glucose-regulated protein 78, Senescence, ROS releasing hydrogel, Tonsil-derived mesenchymal stem cells, Bone regeneration
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
관련분야 논문보기