박윤정 (서울대학교 치과대학)

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서울대학교 치과대학

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Biomaterials, Available online 25 September 2021, 121156 | https://doi.org/10.1016/j.biomaterials.2021.121156 Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78

Da Hyeon Choi^a,1, Kyeong Eun Lee^a,1, Se-Young Oh^b,c, Si Min Lee^d, Beom Soo Jo^e,f, Jue-Yeon Lee^f, Jong-Chul Park^g, Yoon Jeong Park^e,f,*, Ki Dong Park^d,*, Inho Jo^b,c,*, Yoon Shin Park^a,*

^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

형식Research article
게재일2021년 09월 (BRIC 등록일 2021-10-05)
연구진국내 연구진
분야 의약학 > 재생의학

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