Journal article Open Access

Generation of HLA-deficient platelets from hematopoietic progenitor cells: GENERATION OF HLA-DEFICIENT PLTs

Figueiredo, Constança; Goudeva, Lilia; Horn, Peter A.; Eiz-Vesper, Britta; Blasczyk, Rainer; Seltsam, Axel

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    <subfield code="a">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
RNA interference (RNAi)-based approach to silence the
expression of HLA Class I molecules on PLTs derived
from CD34+ progenitor cells. A lentiviral-based system
was used to express short-hairpin RNA (shRNA) targeting
b2-microglobulin (b2m) transcripts in CD34+ progenitor
cells. Differentiation to PLTs was performed by
incubating progenitor cells in the presence of thrombopoietin
and interleukin-3.
RESULTS: The transduction of RNAi cassettes containing
the sequences for shRNAs targeting b2m caused
up to 85% reduction of progenitor cells HLA Class I
antigen expression, which was maintained in the
culture-derived PLTs. The HLA-deficient PLTs derived
from HLA-silenced CD34+ cells proved to be fully functional
in in vitro tests when compared to peripheral
blood–derived PLTs.
CONCLUSIONS: Our data show that in vitro generating
HLA Class I–deficient PLTs from hematopoietic progenitor
cells prove to be feasible. As malignancy risks associated
with insertional mutagenesis are not to be
expected in anucleated PLTs, provision of HLA-deficient
PLTs from large-scale production units may become
reality in the management of patients suffering from
PLT transfusion refractoriness.</subfield>
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    <subfield code="a">Goudeva, Lilia</subfield>
  <datafield tag="700" ind1=" " ind2=" ">
    <subfield code="a">Horn, Peter A.</subfield>
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    <subfield code="a">Eiz-Vesper, Britta</subfield>
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    <subfield code="a">Blasczyk, Rainer</subfield>
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    <subfield code="a">Seltsam, Axel</subfield>
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    <subfield code="a">Figueiredo, Constança</subfield>
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    <subfield code="a">10.1111/j.1537-2995.2010.02644.x</subfield>
    <subfield code="2">doi</subfield>
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    <subfield code="a">Generation of HLA-deficient platelets from hematopoietic progenitor cells: GENERATION OF HLA-DEFICIENT PLTs</subfield>
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