Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78. (November 2021)

• Record Type: Journal Article
• 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
• Is Part Of: Biomaterials. Volume 278(2021)
• Publication Date: 2021-11
• Subjects: Cell surface GRP78+ -- Glucose-regulated protein 78 -- Senescence -- ROS releasing hydrogel -- Tonsil-derived mesenchymal stem cells -- Bone regeneration; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2021.121156
• Languages: English
• ISSNs: 0142-9612

Abstract

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.