Scalable generation of universal platelets from human induced pluripotent stem cells.
Stem Cell Reports
; 3(5): 817-31, 2014 Nov 11.
Article
em En
| MEDLINE
| ID: mdl-25418726
ABSTRACT
Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid "surge" capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the ß2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Megacariócitos
/
Diferenciação Celular
/
Células-Tronco Pluripotentes Induzidas
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos