Naoshi Sugimoto

Naturally occurring CD25(+)CD4(+) regulatory T cells (Tregs) actively engage in the maintenance of immunologic self-tolerance and immunoregulation. They specifically express the transcription factor Forkhead box P3 (Foxp3) as a master control molecule for their development and function. Although several cell-surface molecules have been reported as Treg-specific markers, such as CD25, glucocorticoid-induced TNFR family-related gene/protein and CTL-associated molecule-4, they are also expressed on

Refractoriness to platelet transfusion is a major problem in a small group of patients, and large-scale manufacturing of clinical grade functional platelets ex vivo has remained an elusive goal. Sugimoto et al report on the results of the first clinical trial of an autologous transfusion of induced pluripotent stem cell (iPSC)-derived platelets in a patient who had severe aplastic anemia but no compatible platelet donor. Using methodology described in a complementary article in Blood Advances, t

The ex vivo production of platelets depleted of human leukocyte antigen class I (HLA-I) could serve as a universal measure to overcome platelet transfusion refractoriness caused by HLA-I incompatibility. Here, we developed human induced pluripotent cell-derived HLA-I-deficient platelets (HLA-KO iPLATs) in a clinically applicable imMKCL system by genetic manipulation and assessed their immunogenic properties including natural killer (NK) cells, which reject HLA-I downregulated cells. HLA-KO iPLAT

The recognition of cytoplasmic nucleic acid is critical for innate immune responses against microbial infection and is responsible for autoimmunity induced by dead cells. Here, we report the identification of a unique cytosolic nucleic acid cosensor in human airway epithelial cells and fibroblasts: DEAH (Asp-Glu-Ala-His) box polypeptide 29 (DHX29), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family. Knocking down DHX29 by siRNA attenuated the ability of cells to mount type I IFN and

Human induced pluripotent stem cells (iPSCs) can be limitlessly expanded and differentiated into almost all cell types. Moreover, they are amenable to gene manipulation and, because they are established from somatic cells, can be established from essentially any person. Based on these characteristics, iPSCs have been extensively studied as cell sources for tissue grafts, blood transfusions and cancer immunotherapies, and related clinical trials have started. From an immune-matching perspective,

Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against 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. To produce platelet products for patients with aplastic anemia with allo

Abstract Introduction: Platelet transfusion have saved lives of patients with thrombocytopenia through preventing or treating bleeding complications. Currently, platelet products are provided from blood banks which collect blood from healthy donors. However, our ageing society bears the risk of supply in the future. Furthermore, although the rate is decreasing, alloimmune platelet transfusion refractoriness (allo-PTR) is still found in 5% of platelet transfusion patients. Gestation and previous

Abstract Background Naturally occurring regulatory T cells (Treg) are a subset of CD4+T lymphocytes derived from the thymus. Treg suppress immune responses through multiple mechanisms and are involved in inhibiting the development of autoimmunity. Treg constitutively express the master regulatory gene FOXP3, which is necessary to maintain their phenotype and functions. Human blood circulating FOXP3+ Treg are composed of naïve and activated subsets. CD45RA+CD45RO- naïve Treg enter the blood from

The COVID-19 pandemic has had an enormous impact on multiple facets of human society.1 Although lockdown and similar measures have slowed and limited laboratory research, the shortage of blood products has also drawn much closer attention to the ex vivo production of transfusable blood cells.2,3 Aside from the pandemic, inclement weather or long holidays could also reduce blood donations. Meanwhile, there had already been concerns about platelet product supplies because of their short shelf life

Abstract Each transfusion requires 200-300 billion platelets in patients with thrombocytopenia. To continuously supply such a huge number of platelets by ex vivo generation, two distinct steps, megakaryopoiesis and platelet shedding, must be both considered. For the former, one approach is to increase the number of source cell, megakaryocytes. For example, the immortalized megakaryocyte cell line (imMKCL) system uses self-renewing megakaryocyte (MK) cell lines derived from induced pluripotent st

Abstract Background Platelet transfusion refractoriness (PTR) due to immune factors occurs in 5-15% of thrombocytopenic patients who have received transfusions. The dominant cause of immune PTR is the production of allo-antibodies to human leukocyte antigen (HLA) class I, which is expressed on platelets. In current clinical settings, transfusion of HLA-compatible platelets is the only practical strategy, but their supply is weak due to limited donor source, gives excessive burden on specific don

The COVID-19 pandemic has cast a shadow over transfusion medicine based on the blood donation system. However, managing alloimmune platelet transfusion refractoriness (allo-PTR) has already been difficult. As a first step toward resolving this issue using induced pluripotent stem cell-derived platelet products (iPSC-PLTs), a clinical trial of autologous products (iPLAT1) was conducted in a patient with allo-PTR caused by anti-HPA-1a antibodies who had no compatible donor, and safety was confirme