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Development of platelet replacement therapy using human induced pluripotent stem cells
Author(s) -
Nakamura Sou,
Sugimoto Naoshi,
Eto Koji
Publication year - 2021
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12711
Subject(s) - induced pluripotent stem cell , platelet , haematopoiesis , biology , stem cell , progenitor cell , platelet transfusion , genetic enhancement , immunology , microbiology and biotechnology , gene , genetics , embryonic stem cell
In the body, platelets mainly work as a hemostatic agent, and the lack of platelets can cause serious bleeding. Induced pluripotent stem (iPS) cells potentially allow for a stable supply of platelets that are independent of donors and eliminate the risk of infection. However, a major challenge in iPS cell‐based systems is producing the number of platelets required for a single transfusion (more than 200 billion in Japan). Thus, development in large‐scale culturing technology is required. In previous studies, we generated a self‐renewable, immortalized megakaryocyte cell line by transfecting iPS cell‐derived hematopoietic progenitor cells with c‐MYC, BMI1, and BCL‐XL genes. Optimization of the culture conditions, including the discovery of a novel fluid‐physical factor, turbulence, in the production of platelets in vivo, and the development of bioreactors that apply turbulence have enabled us to generate platelets of clinical quality and quantity. We have further generated platelets deleted of HLA class I expression by using genetic modification technology for patients suffering from alloimmune transfusion refractoriness, since these patients are underserved by current blood donation systems. In this review, we highlight current research and our recent work on iPS cell‐derived platelet induction.