Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads

Hypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism....

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Main Authors: Ha Yeong Kim, Ji Min Seok, Soo Yeon Jung, Min Ji Lee, An Nguyen-Thuy Tran, Seon Ju Yeo, Su A. Park, Han Su Kim
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/2/440
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author Ha Yeong Kim
Ji Min Seok
Soo Yeon Jung
Min Ji Lee
An Nguyen-Thuy Tran
Seon Ju Yeo
Su A. Park
Han Su Kim
author_facet Ha Yeong Kim
Ji Min Seok
Soo Yeon Jung
Min Ji Lee
An Nguyen-Thuy Tran
Seon Ju Yeo
Su A. Park
Han Su Kim
author_sort Ha Yeong Kim
collection DOAJ
description Hypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism. Here, we investigated the feasibility of three-dimensional structural microbeads fabricated with TMSCs and alginate, a natural biodegradable polymer, to treat hypoparathyroidism. Alginate microbeads were fabricated by dropping a 2% (<i>w</i>/<i>v</i>) alginate solution containing TMSCs into a 5% CaCl<sub>2</sub> solution and then differentiated into parathyroid-like cells using activin A and sonic hedgehog for 7 days. The protein expression of PTH, a specific marker of the parathyroid gland, was significantly higher in differentiated alginate microbeads with TMSCs (Al-dT) compared with in undifferentiated alginate microbeads with TMSCs. For in vivo experiments, we created the hypoparathyroidism animal model by parathyroidectomy (PTX) and implanted alginate microbeads in the dorsal interscapular region. The PTX rats with Al-dT (PTX+Al-dT) showed the highest survival rate and weight change and a gradual increase in serum intact PTH levels. We also detected a higher expression of PTH in retrieved tissues of PTX+Al-dT using immunofluorescence analysis. This study demonstrates that alginate microbeads are potential a new tool as a surgically scalable therapy for treating hypoparathyroidism.
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spelling doaj.art-6dcd52e07f3b458d8af1114bd3cd1eab2023-11-23T18:55:36ZengMDPI AGBiomedicines2227-90592022-02-0110244010.3390/biomedicines10020440Development of Surgically Transplantable Parathyroid Hormone-Releasing MicrobeadsHa Yeong Kim0Ji Min Seok1Soo Yeon Jung2Min Ji Lee3An Nguyen-Thuy Tran4Seon Ju Yeo5Su A. Park6Han Su Kim7Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Seoul 07985, KoreaDepartment of Nature-Inspired System and Application, Korea Institute of Machinery and Materials (KIMM), Daejeon 34103, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Seoul 07985, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Seoul 07985, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Seoul 07985, KoreaDepartment of Nature-Inspired System and Application, Korea Institute of Machinery and Materials (KIMM), Daejeon 34103, KoreaDepartment of Nature-Inspired System and Application, Korea Institute of Machinery and Materials (KIMM), Daejeon 34103, KoreaDepartment of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Seoul 07985, KoreaHypoparathyroidism is an endocrine disorder that occurs because of the inability to produce parathyroid hormone (PTH) effectively. Previously, we reported the efficacy of tonsil-derived mesenchymal stem cells (TMSCs) differentiated into parathyroid-like cells for the treatment of hypoparathyroidism. Here, we investigated the feasibility of three-dimensional structural microbeads fabricated with TMSCs and alginate, a natural biodegradable polymer, to treat hypoparathyroidism. Alginate microbeads were fabricated by dropping a 2% (<i>w</i>/<i>v</i>) alginate solution containing TMSCs into a 5% CaCl<sub>2</sub> solution and then differentiated into parathyroid-like cells using activin A and sonic hedgehog for 7 days. The protein expression of PTH, a specific marker of the parathyroid gland, was significantly higher in differentiated alginate microbeads with TMSCs (Al-dT) compared with in undifferentiated alginate microbeads with TMSCs. For in vivo experiments, we created the hypoparathyroidism animal model by parathyroidectomy (PTX) and implanted alginate microbeads in the dorsal interscapular region. The PTX rats with Al-dT (PTX+Al-dT) showed the highest survival rate and weight change and a gradual increase in serum intact PTH levels. We also detected a higher expression of PTH in retrieved tissues of PTX+Al-dT using immunofluorescence analysis. This study demonstrates that alginate microbeads are potential a new tool as a surgically scalable therapy for treating hypoparathyroidism.https://www.mdpi.com/2227-9059/10/2/440hypoparathyroidismalginatemicrobeadstonsil-derived mesenchymal stem cellsparathyroid hormone
spellingShingle Ha Yeong Kim
Ji Min Seok
Soo Yeon Jung
Min Ji Lee
An Nguyen-Thuy Tran
Seon Ju Yeo
Su A. Park
Han Su Kim
Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
Biomedicines
hypoparathyroidism
alginate
microbeads
tonsil-derived mesenchymal stem cells
parathyroid hormone
title Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
title_full Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
title_fullStr Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
title_full_unstemmed Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
title_short Development of Surgically Transplantable Parathyroid Hormone-Releasing Microbeads
title_sort development of surgically transplantable parathyroid hormone releasing microbeads
topic hypoparathyroidism
alginate
microbeads
tonsil-derived mesenchymal stem cells
parathyroid hormone
url https://www.mdpi.com/2227-9059/10/2/440
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