Sustained release of parathyroid hormone via in situ cross-linking gelatin hydrogels improves the therapeutic potential of tonsil-derived mesenchymal stem cells for hypoparathyroidism.
J Tissue Eng Regen Med. 2018 Mar;12(3):e1747-e1756. doi: 10.1002/term.2430. Epub 2017 Jun 27.
Park YS1,2,3, Lee Y4, Jin YM1,2, Kim G1,2, Jung SC2,5, Park YJ6, Park KD4, Jo I1,2.
- 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.
- Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
- Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
- Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
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.