Transfer to the clinic: refining forward programming of hPSCs to megakaryocytes for platelet production in bioreactors.
Blood Adv
; 5(7): 1977-1990, 2021 04 13.
Article
en En
| MEDLINE
| ID: mdl-33843988
ABSTRACT
The production of in vitro-derived platelets has great potential for transfusion medicine. Here, we build on our experience in the forward programming (FoP) of human pluripotent stem cells (hPSCs) to megakaryocytes (MKs) and address several aspects of the complex challenges to bring this technology to the bedside. We first identify clinical-grade hPSC lines that generate MKs efficiently. We design a bespoke media to maximize both production and maturity of MKs and improve platelet output. Crucially, we transition the lentiviral-based FoP of hPSCs to a nonviral inducible system. We also show how small molecules promote a definitive hematopoiesis phenotype during the differentiation process, thereby increasing the quality of the final product. Finally, we generate platelets using a bioreactor designed to reproduce the physical cues that promote platelet production in the bone marrow. We show that these platelets are able to contribute to both thrombus formation in vitro and have a hemostatic effect in thrombocytopenic mice in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Megacariocitos
/
Células Madre Pluripotentes
Límite:
Animals
Idioma:
En
Revista:
Blood Adv
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido