Generation of HLA‐deficient platelets from hematopoietic progenitor cells

  title={Generation of HLA‐deficient platelets from hematopoietic progenitor cells},
  author={Constança Figueiredo and Lilia Goudeva and Peter A. Horn and Britta Eiz-Vesper and Rainer Blasczyk and Axel Seltsam},
BACKGROUND: Exposure to allogeneic blood products often leads to the development of human leukocyte antigen (HLA) antibodies. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA Class I antigens constitutes a significant clinical problem. 

HLA‐selected platelets for platelet refractory patients with HLA antibodies: a single‐center experience

Platelet refractoriness due to HLA immunization represents a problem in transfusion management of thrombocytopenic hematology patients and how the degree of HLA mismatch influences transfusion outcome is poorly studied.

Bone marrow stromal cells transduced with a thrombopoietin, interleukin‐6, and interleukin‐11 syncretic gene induce cord mononuclear cells to generate platelets in vitro

The induction of hematopoietic stem cells to produce mass numbers of platelets (PLTs) in vitro is an effective method to address a lack of PLTs and PLT transfusion resistance in the clinic. However,

A more efficient preparation system for HLA‐eliminated platelets

The HLA‐eliminated platelets production process is improved by employing a hollow‐fibre system at the last step of the production process after an acid and a reaction buffer have been washed out conventionally by centrifugation.

HLA-Universal Platelet Transfusions Prevent Platelet Refractoriness in a Mouse Model

The capacity of HLA-silenced PLTs to escape HLA antibody-mediated cytotoxicity in vitro and in vivo is assessed and it is shown that the generation of functional HLA class I-silence PLTs from CD34+ cells, using a short hairpin RNA (shRNA) to target β2-microglobulin (β2m) transcripts, is feasible.

Generation and characterization of HLA-universal platelets derived from induced pluripotent stem cells

Generating functional iPSC-derived platelets in vitro without HLA class I expression by knocking out the β2m gene using paired CRISPR/Cas9 nickases is successfully generated.

Semaphorin 7A inhibits platelet production from CD34+ progenitor cells

The effect of Sema7A on differentiation of CD34+ progenitor cells into megakaryocytes and platelets is investigated and it is found that it has regulatory effects on blood cell differentiation via its receptors β1‐integrin and plexin C1.

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

In vitro produced low immunogenic MKs and PLTs may become an alternative to PLT donation in PLT-based therapies and an important component in the management of severe alloimmunized patients.

A future with less HLA: potential clinical applications of HLA-universal cells.

A strategy to decrease the immunogenicity of cell and tissues to improve their survival after allogeneic transplantation in the absence of immunosuppression is developed.

The source of HLA molecules on platelets: Does platelets adsorb soluble HLA molecules from their environment?

Platelets were unable to significantly adsorb exogenous HLA antigens from their environment and further studies are needed to unravel the nature and origin of HLA molecules on platelets.

Generation of HLA Universal Megakaryocytes and Platelets by Genetic Engineering

Genetically engineered HLA-silenced MKs and PLTs were shown to be functional and to have the capability to survive cell- and antibody-mediated cytotoxicity using in vitro and in vivo models.



HLA class I‐eluted platelets as an alternative to HLA‐matched platelets

BACKGROUND: Alloimmunized refractory thrombocytopenic patients often require HLA‐matched platelet transfusions. As the HLA system is very polymorphic, sufficient HLA‐matched donors are not available

An alloimmunized, thrombocytopenic patient successfully transfused with acid‐treated, random‐donor platelets

Alloimmunized, thrombocytopenic patients, refractory to random‐donor platelet transfusion, often respond to HLA‐identical single‐donation platelets, which are expensive, take time to prepare, and donors are sometimes not to be found.

A genetic strategy to control expression of human blood group antigens in red blood cells generated in vitro

BACKGROUND: The ability to generate red blood cells of a chosen blood group phenotype would be a major advance in transfusion when considering low‐ and high‐frequency blood group antigens.

Incidence and specificity of HLA antibodies in multitransfused patients with acquired aplastic anemia

BACKGROUND:  This study aimed to establish the prevalence and characteristics of anti‐HLA in antibody acquired aplastic anemia patients following cessation of antithymocyte globulin therapy and to


This work presents the case of a 34-year-old woman with a diagnosis of chronic myeloid leukaemia in the aplastic phase of an allogeneic bone marrow transplant, who became refractory to platelet transfusions after several transfusions.

Gene therapy for severe combined immunodeficiency: are we there yet?

In this review, the advantages and limitations associated with the use of gene therapy to cure SCID are summarized and insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are discussed.

In vitro clinical‐grade generation of red blood cells from human umbilical cord blood CD34+ cells

In vitro generation of clinically available RBCs from hematopoietic stem cells could be a promising new source to supplement the blood supply as there is no appropriate alternative source of red blood cells to relieve the worsening shortage of blood available for transfusion.

The kinetics of HLA class I elution and the relevance for the use of HLA‐eluted platelet transfusions

Factors which influenced the HLA reduction by flow cytometry were investigated, resulting in an almost complete removal of HLA class I molecules from the site of the intracytoplasmatic part of the heavy chain.

Profound thrombocytopenia and survival of hematopoietic stem cell transplant patients without clinically significant bleeding, using prophylactic platelet transfusion triggers of 10 × 109 or 20 × 109 per L

A retrospective analysis evaluates thrombocytopenia and survival of 381 hematopoietic stem cell transplant (HSCT) patients without clinically significant bleeding, with 10 × 109 and 20’ד109 per L prophylactic triggers.

Effects of cytokines on platelet production from blood and marrow CD34+ cells.

The data show that this culture system may be useful to study the effects of cytokines and the role of polyploidization on platelet production and function and suggests that proplatelet formation may be inhibited by non-MK cells which contaminate the cultures when the entire CD34+ cell population is used.