Sustained release of parathyroid hormone via in situ cross-linking gelatin hydrogels improves the therapeutic potential of tonsil-derived mesenchymal stem cells for hypoparathyroidism

Yoon Shin Park, Yunki Lee, Yoon Mi Jin, Gyungah Kim, Sung Chul Jung, Yoon Jeong Park, Ki Dong Park, Inho Jo

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)e1747-e1756
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • gelatin hydrogels
  • hypoparathyroidism
  • ionized calcium
  • parathyroid hormone
  • parathyroidectomized animal
  • tonsil-derived mesenchymal stem cells

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