RRC ID |
73129
|
著者 |
Sugimoto N, Nakamura S, Shimizu S, Shigemasa A, Kanda J, Matsuyama N, Tanaka M, Hayashi T, Fuchizaki A, Nogawa M, Watanabe N, Okamoto S, Handa M, Sawaguchi A, Momose D, Koh KR, Tani Y, Takaori-Kondo A, Eto K.
|
タイトル |
Production and nonclinical evaluation of an autologous iPSC-derived platelet product for the iPLAT1 clinical trial.
|
ジャーナル |
Blood Adv
|
Abstract |
Donor-derived platelets are provided to treat or prevent hemorrhage in patients with thrombocytopenia. However, approximately 5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against class I human leukocyte antigens (HLA-I) or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. Aiming to produce platelet products for an aplastic anemia patient with allo-PTR due to rare HPA-1 mismatch in Japan, we have developed an ex vivo good manufacturing process (GMP)-based production system for an induced pluripotent stem cell-derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent clone was selected for the master cell bank (MCB) and confirmed for safety including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive non-clinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report displays a complete system for the GMP-based production of iPSC-PLTs and the required non-clinical studies, and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs, in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products which use iPSC-derived progenitor cells as an MCB.
|
巻・号 |
6(23)
|
ページ |
6056-6069
|
公開日 |
2022-12-13
|
DOI |
10.1182/bloodadvances.2022008512
|
PII |
486697
|
PMID |
36149941
|
PMC |
PMC9706535
|
MeSH |
Animals
Antigens, Human Platelet*
Blood Platelets / metabolism
Hematopoietic Stem Cell Transplantation* / adverse effects
Humans
Induced Pluripotent Stem Cells* / metabolism
Platelet Transfusion / adverse effects
Rabbits
Thrombocytopenia* / etiology
|
IF |
4.91
|
リソース情報 |
遺伝子材料 |
pcDNA3 Venus-Akaluc (RDB15781) |