Anti-fibrotic effect of a selective estrogen receptor modulator in systemic sclerosis.
Stem Cell Res Ther
; 13(1): 303, 2022 07 15.
Article
em En
| MEDLINE
| ID: mdl-35841004
BACKGROUND: The rarity of systemic sclerosis (SSc) has hampered the development of therapies for this intractable autoimmune disease. Induced pluripotent stem cell (iPSC) can be differentiated into the key disease-affected cells in vitro. The generation of patient-derived iPSCs has opened up possibilities for rare disease modeling. Since these cells can recapitulate the disease phenotypes of the cell in question, they are useful high-throughput platforms for screening for drugs that can reverse these abnormal phenotypes. METHODS: SSc iPSC was generated from PBMC by Sendai virus. Human iPSC lines from SSc patients were differentiated into dermal fibroblasts and keratinocytes. The iPSC-derived differentiated cells from the SSc patients were used on high-throughput platforms to screen for FDA-approved drugs that could be effective treatments for SSc. RESULTS: Skin organoids were generated from these cells exhibited fibrosis that resembled SSc skin. Screening of the 770-FDA-approved drug library showed that the anti-osteoporotic drug raloxifene reduced SSc iPSC-derived fibroblast proliferation and extracellular matrix production and skin fibrosis in organoids and bleomycin-induced SSc-model mice. CONCLUSIONS: This study reveals that a disease model of systemic sclerosis generated using iPSCs-derived skin organoid is a novel tool for in vitro and in vivo dermatologic research. Since raloxifene and bazedoxifene are well-tolerated anti-osteoporotic drugs, our findings suggest that selective estrogen receptor modulator (SERM)-class drugs could treat SSc fibrosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Escleroderma Sistêmico
/
Dermatopatias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cell Res Ther
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Coréia do Sul