Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78
- 주제(키워드) Cell surface GRP78 , Glucose-regulated protein 78 , Senescence , ROS releasing hydrogel , Tonsil-derived mesenchymal stem cells , Bone regeneration
- 주제(기타) Engineering, Biomedical; Materials Science, Biomaterials
- 설명문(일반) [Choi, Da Hyeon; Lee, Kyeong Eun; Park, Yoon Shin] Chungbuk Natl Univ, Coll Nat Sci, Sch Biol Sci, Dept Biol Sci & Biotechnol, Cheongju 28644, South Korea; [Oh, Se-Young; Jo, Inho] Ewha Womans Univ, Coll Med, Dept Mol Med, 25 Magokdong Ro 2 Gil, Seoul 07804, South Korea; [Oh, Se-Young; Jo, Inho] Ewha Womans Univ, Grad Program Syst Hlth Sci & Engn, 25 Magokdong Ro 2 Gil, Seoul 07804, South Korea; [Lee, Si Min; Park, Ki Dong] Ajou Univ, Dept Mol Sci & Technol, 206 World Cup Ro, Suwon 16499, Gyeonggi Do, South Korea; [Jo, Beom Soo; Park, Yoon Jeong] Seoul Natl Univ, Sch Dent, Dept Dent Regenerat Bioengn, Seoul 03080, South Korea; [Jo, Beom Soo; Park, Yoon Jeong] Seoul Natl Univ, Sch Dent, Dent Res Inst, Seoul 03080, South Korea; [Jo, Beom Soo; Lee, Jue-Yeon; Park, Yoon Jeong] Nano Intelligent Biomed Engn Corp NIBEC, Cent Res Inst, 404 Biomat Res Bldg,101 Daehak Ro, Seoul 03080, South Korea; [Park, Jong-Chul] Yonsei Univ, Dept Med Engn, Cellbiocontrol Lab, Coll Med, Seoul 03722, South Korea
- 등재 SCIE, SCOPUS
- OA유형 hybrid
- 발행기관 ELSEVIER SCI LTD
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183669
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.biomaterials.2021.121156
- PubMed https://pubmed.ncbi.nlm.nih.gov/34597900
초록/요약
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 beta-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.
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