"Platelet transfusion refractory", which occurs in about 5% of platelet transfusion patients, is rejected if the platelet type (HLA class I) does not match.Since 9 types of HLA class I are required to cover about 140% of Japanese people, the development of "universal" platelet preparations that can be transfused regardless of the type of HLA class I has been considered.

 This time, researchers at the Center for iPS Cell Research and Application, Kyoto University, and the Research Center for Regenerative Medicine, Chiba University have succeeded in developing iPS platelets lacking the expression of HLA class I (HLA-deficient iPS platelets).Furthermore, through joint research with Kumamoto University, HLA deficiency is found in both anti-HLA antibodies that cause platelet transfusion refractory and NK cells that are known to attack cells with reduced expression of HLA class I. It was demonstrated in vivo in an animal model that lost iPS platelets circulate in the body without being attacked.

 So far, the researchers have succeeded in inducing megakaryocytes that produce platelets from human iPS cells, and have created an immortalized megakaryocyte strain (imMKCL) that is capable of self-renewal and can be cryopreserved in vitro. Has been successful.This time, we succeeded in producing HLA-deficient iPS platelets by producing imMKCL from iPS cells lacking HLA class I constituent molecules by genome editing.

 It was confirmed that HLA-deficient iPS platelets are equivalent in quality and function to iPS platelets that have not undergone HLA-deficient manipulation, and platelet transfusion refractory is reproduced in a mouse model with newly established human immune cells. Even in this state, it was not affected by any of the anti-HLA antibodies and NK cells.It is said that iPS platelets did not induce the attack activity of NK cells regardless of the presence or absence of HLA, and it was also found that platelets are not attacked by NK cells even if they do not express HLA class I.

 The clinical application of HLA-deficient iPS platelets is expected to be the basis for the industrialization of iPS platelets that can be transfused to all.

Paper information:[Stem Cell Reports] iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity

Kyoto University

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With the motto of self-study, we will continue to maintain a free academic style that is not bound by common sense, and develop human resources who have both creativity and practical ability.We provide an inclusive learning space that allows for diverse and hierarchical choices so that students themselves can choose a solid future through valuable trial and error. […]

Chiba University

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Chiba University has 10 faculties, 7 graduate schools / faculties, and a large number of affiliated facilities, and has specialized knowledge and skills, high problem-solving ability, high intelligence, ethical standards, and rich humanity, and has an interdisciplinary perspective. We aim to develop human resources who can play an active role internationally.Actively promote the enhancement of liberal arts education and the internationalization of educational activities, which are the basis of this […]

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