title: Sustained release of parathyroid hormone via in situ cross-linking gelatin hydrogels improves the therapeutic potential of tonsil-derived mesenchymal stem cells for hypoparathyroidism.
abstract: Biomimetic parathyroid regeneration with sustained release of parathyroid hormone (PTH) into the blood stream is a considerable challenge in hypoparathyroidism treatment. We recently reported that tonsil-derived mesenchymal stem cells (TMSCs), if these cells were both differentiated in vitro before implantation and incorporated into a scaffold Matrigel, are a good cell source for parathyroid regeneration in a parathyroidectomized (PTX) animal model. Here, we present a new strategy for improved clinical application that enhances the sustained release of PTH by controlling mechanical stiffness using in situ-forming gelatin-hydroxyphenyl propionic acid (GH) hydrogels (GHH). Differentiated TMSCs (dTMSCs) embedded in a GHH with a strength of 4.4 kPa exhibited the best sustained release of PTH and were the most effective in hypoparathyroidism treatment, showing improved blood calcium homeostasis compared with Matrigel-embedded dTMSCs. Interestingly, undifferentiated control TMSCs (cTMSCs) also released PTH in a sustained manner if incorporated into GHH. Collectively, these findings may establish a new paradigm for parathyroid regeneration that could ultimately evolve into an improved clinical application. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.|Ewha Tonsil-derived Mesenchymal Stem Cells Research Center (ETSRC), School of Medicine, Ewha Womans University, Seoul, Republic of Korea.|School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Yoon Shin
authors.identifier: 0000-0002-5373-9218
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Yunki
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.|Ewha Tonsil-derived Mesenchymal Stem Cells Research Center (ETSRC), School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Yoon Mi
authors.initials: YM
authors.lastname: Jin
authors.affiliation: Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.|Ewha Tonsil-derived Mesenchymal Stem Cells Research Center (ETSRC), School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Gyungah
authors.initials: G
authors.lastname: Kim
authors.affiliation: Ewha Tonsil-derived Mesenchymal Stem Cells Research Center (ETSRC), School of Medicine, Ewha Womans University, Seoul, Republic of Korea.|Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Jung
authors.affiliation: Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yoon Jeong
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
authors.forename: Ki Dong
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.|Ewha Tonsil-derived Mesenchymal Stem Cells Research Center (ETSRC), School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Inho
authors.identifier: 0000-0001-6060-6416
authors.initials: I
authors.lastname: Jo
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005780:Gelatin / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007011:Hypoparathyroidism / Q000097:blood / Q000628:therapy*; D020007:Implants, Experimental; D007700:Kinetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018919:Neovascularization, Physiologic; D014066:Palatine Tonsil / Q000166:cytology*; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D011422:Propionates / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D013552:Swine
chemical_list: D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D010281:Parathyroid Hormone; D011422:Propionates; D005780:Gelatin; C029658:propionic acid; D002118:Calcium
keywords: gelatin hydrogels; hypoparathyroidism; ionized calcium; parathyroid hormone; parathyroidectomized animal; tonsil-derived mesenchymal stem cells