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Sustained release of parathyroid hormone via in situ cross‐linking gelatin hydrogels improves the therapeutic potential of tonsil‐derived mesenchymal stem cells for hypoparathyroidism
Author(s) -
Park Yoon Shin,
Lee Yunki,
Jin Yoon Mi,
Kim Gyungah,
Jung Sung Chul,
Park Yoon Jeong,
Park Ki Dong,
Jo Inho
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2430
Subject(s) - parathyroid hormone , mesenchymal stem cell , hypoparathyroidism , chemistry , parathyroid chief cell , regeneration (biology) , medicine , self healing hydrogels , endocrinology , microbiology and biotechnology , calcium , biology , organic chemistry
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.