更新于：2024-11-01

CD49d x TfR1

更新于：2024-11-01

基本信息

关联

项与 CD49d x TfR1 相关的药物

TE-5200

靶点

CD49d x TfR1

作用机制

CD49d拮抗剂 [+1]

在研机构

免疫功坊股份有限公司

原研机构

免疫功坊股份有限公司

在研适应症

多发性硬化症

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CD49d x TfR1 相关的临床结果

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100 项与 CD49d x TfR1 相关的转化医学

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0 项与 CD49d x TfR1 相关的专利（医药）

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项与 CD49d x TfR1 相关的文献（医药）

2024-03-29·Journal of Leukocyte Biology

Human CD34+/dim neutrophil-committed progenitors do not differentiate into neutrophil-like CXCR1+CD14+CD16− monocytes in vitro

Article

作者: Finotti, Giulia ; Gasperini, Sara ; Gardiman, Elisa ; Calzetti, Federica ; Tecchio, Cristina ; Signoretto, Ilaria ; Bianchetto-Aguilera, Francisco ; Tamassia, Nicola ; Cassatella, Marco A

AbstractThe advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSCloCD66b+CD15+CD11b−CD49dhiproNeu1s, SSChiCD66b+CD15+CD11b−CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101−preNeus, and Lin−CD66b+CD117+CD71+eNePs. In this research field, we recently identified CD66b−CD38+CD64dimCD115−, CD34+, and CD34dim/− cells exclusively committed to the neutrophil lineage (which we renamed as CD34+ and CD34dim/− neutrophil-committed progenitors), representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify 4 populations of neutrophil-committed progenitors: CD34+CD45RA−/NCP1s, CD34+CD45RA+/NCP2s, CD34dim/−CD45RA+/NCP3s, and CD34dim/−CD45RA−/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors, termed either neutrophil progenitors or “early neutrophil-committed progenitors,” would generate immunosuppressive neutrophil-like CXCR1+CD14+CD16− monocytes. Hence, presuming that neutrophil progenitors/“early neutrophil-committed progenitors” correspond to neutrophil-committed progenitors, the selective neutrophil commitment that we attributed to neutrophil-committed progenitors is contradicted by Ikeda and coworkers’ article. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by neutrophil-committed progenitors 2 and 4 (selected as representatives of neutrophil-committed progenitors), we categorically exclude that neutrophil-committed progenitors generate neutrophil-like CXCR1+CD14+CD16− monocytes. Rather, we provide substantial evidence indicating that the cells generated by neutrophil progenitors/“early neutrophil-committed progenitors” are neutrophilic cells at a different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1+CD14+CD16− monocytes, as pointed by Ikeda and coworkers. Hence, the conclusion that neutrophil progenitors/“early neutrophil-committed progenitors” aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation.

2022-05-01·Cytometry Part A4区 · 生物学

Phenotypic analysis of erythrocytes in sickle cell disease using imaging flow cytometry

4区 · 生物学

Article

作者: St. John, Alexander E. ; Chen, Junmei ; López, José A. ; Özpolat, Tahsin ; Chang, Tim C. ; Konkle, Barbara A. ; Wu, Xiaoping

AbstractThe morphology and other phenotypic characteristics of erythrocytes in sickle cell disease (SCD) have been analyzed for decades in patient evaluation. This involves a variety of techniques, including microscopic analysis of stained blood films, flow cytometry, and cell counting. Here, we analyzed SCD blood using imaging flow cytometry (IFC), a technology that combines flow cytometry and microscopy to enable simultaneous rapid‐throughput analysis of cellular morphology and cell‐surface markers. With IFC, we were able to automate quantification of poikilocytes from SCD blood. An important subpopulation of poikilocytes represented dense cells, although these could not be distinguished from other poikilocytes without first centrifuging the blood through density gradients. In addition, CD71‐positive RBCs from SCD patients had two subpopulations: one with high CD71 expression and a puckered morphology and another with lower CD71 expression and biconcave morphology and presumably representing a later stage of differentiation. Some RBCs with puckered morphologies that were strongly positive for DAPI and CD49d were in fact nucleated RBCs. IFC identified more phosphatidylserine‐expressing red cells in SCD than did conventional flow cytometry and these could also be divided into two subpopulations. One population had diffuse PS expression and appeared to be composed primarily of RBC ghosts; the other had lower overall PS expression present in intense, punctate dots overlying Howell‐Jolly bodies. This study demonstrates that IFC can rapidly reveal and quantify RBC features in SCD that require numerous tedious methods to identify conventionally. Thus, IFC is likely to be a useful technique for evaluating and monitoring SCD.

2022-02-01·American Journal of Hematology

Erythropoietic properties of human induced pluripotent stem cells‐derived red blood cells in immunodeficient mice

Article

作者: Jaye, David ; Roback, John D. ; Jajosky, Ryan ; Deng, Qiaomei ; Deng, Jiusheng ; Stowell, Sean R. ; Gao, Yongxing ; Cheng, Linzhao ; Lancelot, Moira ; Deeb, Kristin ; Saakadze, Natia ; Liu, Senquan

AbstractTransfusion of red blood cells (RBCs) is a life‐saving intervention for anemic patients. Human induced pluripotent stem cells (iPSC) have the capability to expand and differentiate into RBCs (iPSC‐RBCs). Here we developed a murine model to investigate the in vivo properties of human iPSC‐RBCs. iPSC lines were produced from human peripheral blood mononuclear cells by transient expression of plasmids containing OCT4, SOX2, MYC, KLF4, and BCL‐XL genes. Human iPSC‐RBCs were generated in culture supplemented with human platelet lysate, and were CD34−CD235a+ CD233+ CD49dlow CD71low; about 13% of iPSC‐RBCs were enucleated before transfusion. Systemic administration of clodronate liposomes (CL) and cobra venom factor (CVF) to NOD scid gamma (NSG) mice markedly promoted the circulatory survival of human iPSC‐RBCs following transfusion. While iPSC‐RBCs progressively decreased with time, 90% of circulating iPSC‐RBCs were enucleated 1 day after transfusion (CD235a+ CD233+ CD49d− CD71−). Surprisingly, human iPSC‐RBCs reappeared in the peripheral circulation at 3 weeks after transfusion at levels more than 8‐fold higher than at 1 h after transfusion. Moreover, a substantial portion of the transfused nucleated iPSC‐RBCs preferentially homed to the bone marrow, and were detectable at 24 days after transfusion. These results suggest that nucleated human iPSC‐derived cells that homed to the bone marrow of NSG mice retained the capability to complete differentiation into enucleated erythrocytes and egress the bone marrow into peripheral blood. The results offer a new model using human peripheral blood‐derived iPSC and CL/CVF‐treated NSG mice to investigate the development and circulation of human erythroid cells in vivo.