Small molecule inhibitors and culture conditions enhance therapeutic cell and EV potency via activation of beta-catenin and suppression of THY1.
Nanomedicine
; 33: 102347, 2021 04.
Article
em En
| MEDLINE
| ID: mdl-33321216
ABSTRACT
Primary cell therapy continues to face significant hurdles to therapeutic translation including the inherent variations that exist from donor to donor, batch to batch, and scale-up driven modifications to the manufacturing process. Cardiosphere-derived cells (CDCs) are stromal/progenitor cells with clinically demonstrated tissue reparative capabilities. Mechanistic investigations have identified canonical Wnt/ß-catenin signaling as a therapeutic potency marker, and THY1 (CD90) expression as inversely correlated with potency. Here we demonstrate that the cardiosphere formation process increases ß-catenin levels and enriches for therapeutic miR content in the extracellular vesicles of these cells, namely miR-146a and miR-22. We further find that loss of potency is correlated with impaired cardiosphere formation. Finally, our data show that small GSK3ß inhibitors including CHIR, and BIO and "pro-canonical Wnt" culturing conditions can rescue ß-catenin signaling and reduce CD90 expression. These findings identify strategies that could be used to maintain CDC potency and therapeutic consistency.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
/
Biomarcadores
/
Antígenos Thy-1
/
Quinases de Proteína Quinase Ativadas por Mitógeno
/
Quinases da Glicogênio Sintase
/
Difenilamina
/
Beta Catenina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nanomedicine
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos