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Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome

INTRODUCTION: Pendred syndrome is an autosomal-recessive disease characterized by congenital hearing loss and thyroid goiter. Previously, cell stress susceptibilities were shown to increase in patient-derived cells with intracellular aggregation using an in vitro acute cochlear cell model derived fr...

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Autores principales: Hosoya, Makoto, Saeki, Tsubasa, Saegusa, Chika, Matsunaga, Tatsuo, Okano, Hideyuki, Fujioka, Masato, Ogawa, Kaoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society for Regenerative Medicine 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299162/
https://www.ncbi.nlm.nih.gov/pubmed/30581897
http://dx.doi.org/10.1016/j.reth.2018.11.001
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author Hosoya, Makoto
Saeki, Tsubasa
Saegusa, Chika
Matsunaga, Tatsuo
Okano, Hideyuki
Fujioka, Masato
Ogawa, Kaoru
author_facet Hosoya, Makoto
Saeki, Tsubasa
Saegusa, Chika
Matsunaga, Tatsuo
Okano, Hideyuki
Fujioka, Masato
Ogawa, Kaoru
author_sort Hosoya, Makoto
collection PubMed
description INTRODUCTION: Pendred syndrome is an autosomal-recessive disease characterized by congenital hearing loss and thyroid goiter. Previously, cell stress susceptibilities were shown to increase in patient-derived cells with intracellular aggregation using an in vitro acute cochlear cell model derived from patient-specific pluripotent stem (iPS) cells. Moreover, we showed that rapamycin can relieve cell death. However, studies regarding long-term cell survival without cell stressors that mimic the natural course of disease or the rational minimum concentration of rapamycin that prevents cell death are missing. METHODS: In this report, we first investigated the rational minimum concentration of rapamycin using patient-specific iPS cells derived-cochlear cells with three different conditions of acute stress. We next confirmed the effects of rapamycin in long-term cell survival and phenotypes by using cochlear cells derived from three different patient-derived iPS cells. RESULTS: We found that inner ear cells derived from Pendred syndrome patients are more vulnerable than those from healthy individuals during long-term culturing; however, this susceptibility was relieved via treatment with low-dose rapamycin. The slow progression of hearing loss in patients may be explained, in part, by the vulnerability observed in patient cells during long-term culturing. We successfully evaluated the rational minimum concentration of rapamycin for treatment of Pendred syndrome. CONCLUSION: Our results suggest that low-dose rapamycin not only decreases acute symptoms but may prevent progression of hearing loss in Pendred syndrome patients.
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spelling pubmed-62991622018-12-21 Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome Hosoya, Makoto Saeki, Tsubasa Saegusa, Chika Matsunaga, Tatsuo Okano, Hideyuki Fujioka, Masato Ogawa, Kaoru Regen Ther Original Article INTRODUCTION: Pendred syndrome is an autosomal-recessive disease characterized by congenital hearing loss and thyroid goiter. Previously, cell stress susceptibilities were shown to increase in patient-derived cells with intracellular aggregation using an in vitro acute cochlear cell model derived from patient-specific pluripotent stem (iPS) cells. Moreover, we showed that rapamycin can relieve cell death. However, studies regarding long-term cell survival without cell stressors that mimic the natural course of disease or the rational minimum concentration of rapamycin that prevents cell death are missing. METHODS: In this report, we first investigated the rational minimum concentration of rapamycin using patient-specific iPS cells derived-cochlear cells with three different conditions of acute stress. We next confirmed the effects of rapamycin in long-term cell survival and phenotypes by using cochlear cells derived from three different patient-derived iPS cells. RESULTS: We found that inner ear cells derived from Pendred syndrome patients are more vulnerable than those from healthy individuals during long-term culturing; however, this susceptibility was relieved via treatment with low-dose rapamycin. The slow progression of hearing loss in patients may be explained, in part, by the vulnerability observed in patient cells during long-term culturing. We successfully evaluated the rational minimum concentration of rapamycin for treatment of Pendred syndrome. CONCLUSION: Our results suggest that low-dose rapamycin not only decreases acute symptoms but may prevent progression of hearing loss in Pendred syndrome patients. Japanese Society for Regenerative Medicine 2018-12-17 /pmc/articles/PMC6299162/ /pubmed/30581897 http://dx.doi.org/10.1016/j.reth.2018.11.001 Text en © 2019 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Hosoya, Makoto
Saeki, Tsubasa
Saegusa, Chika
Matsunaga, Tatsuo
Okano, Hideyuki
Fujioka, Masato
Ogawa, Kaoru
Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
title Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
title_full Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
title_fullStr Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
title_full_unstemmed Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
title_short Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
title_sort estimating the concentration of therapeutic range using disease-specific ips cells: low-dose rapamycin therapy for pendred syndrome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299162/
https://www.ncbi.nlm.nih.gov/pubmed/30581897
http://dx.doi.org/10.1016/j.reth.2018.11.001
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