Generation and manipulation of human iPSC-derived platelets.
Cell Mol Life Sci
; 78(7): 3385-3401, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-33439272
ABSTRACT
The discovery of iPSCs has led to the ex vivo production of differentiated cells for regenerative medicine. In the case of transfusion products, the derivation of platelets from iPSCs is expected to complement our current blood-donor supplied transfusion system through donor-independent production with complete pathogen-free assurance. This derivation can also overcome alloimmune platelet transfusion refractoriness by resulting in autologous, HLA-homologous or HLA-deficient products. Several developments were necessary to produce a massive number of platelets required for a single transfusion. First, expandable megakaryocytes were established from iPSCs through transgene expression. Second, a turbulent-type bioreactor with improved platelet yield and quality was developed. Third, novel drugs that enabled efficient feeder cell-free conditions were developed. Fourth, the platelet-containing suspension was purified and resuspended in an appropriate buffer. Finally, the platelet product needed to be assured for competency and safety including non-tumorigenicity through in vitro and in vivo preclinical tests. Based on these advancements, a clinical trial has started. The generation of human iPSC-derived platelets could evolve transfusion medicine to the next stage and assure a ubiquitous, safe supply of platelet products. Further, considering the feasibility of gene manipulations in iPSCs, other platelet products may bring forth novel therapeutic measures.
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Base de dados:
MEDLINE
Assunto principal:
Plaquetas
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Transfusão de Sangue
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Megacariócitos
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Medicina Regenerativa
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Células-Tronco Pluripotentes Induzidas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article