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.
|Journal||Journal of Tissue Engineering and Regenerative Medicine|
|State||Published - Mar 2018|
Bibliographical noteFunding Information:
This study was supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012M3A9C6049728, NRF-2017R1A2B4002611, and NRF-2015R1A2A1A14027221), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), of the Ministry of Health & Welfare, Republic of Korea (HI14C-1557).
Copyright © 2017 John Wiley & Sons, Ltd.
- gelatin hydrogels
- ionized calcium
- parathyroid hormone
- parathyroidectomized animal
- tonsil-derived mesenchymal stem cells