PMID- 20412529
OWN - NLM
STAT- MEDLINE
DCOM- 20101022
LR  - 20101004
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Linking)
VI  - 50
IP  - 8
DP  - 2010 Aug
TI  - Generation of HLA-deficient platelets from hematopoietic progenitor cells.
PG  - 1690-701
LID - 10.1111/j.1537-2995.2010.02644.x [doi]
AB  - 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. STUDY DESIGN AND METHODS: We developed an 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 beta2-microglobulin (beta2m) 
      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 beta2m 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.
CI  - (c) 2010 American Association of Blood Banks.
FAU - Figueiredo, Constanca
AU  - Figueiredo C
AD  - Institute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
FAU - Goudeva, Lilia
AU  - Goudeva L
FAU - Horn, Peter A
AU  - Horn PA
FAU - Eiz-Vesper, Britta
AU  - Eiz-Vesper B
FAU - Blasczyk, Rainer
AU  - Blasczyk R
FAU - Seltsam, Axel
AU  - Seltsam A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100415
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Gene Silencing
MH  - Hematopoietic Stem Cells/*cytology
MH  - Histocompatibility Antigens Class I/*physiology
MH  - Humans
MH  - Megakaryocytes/*immunology
MH  - *Platelet Transfusion
MH  - RNA Interference
MH  - beta 2-Microglobulin/antagonists & inhibitors
EDAT- 2010/04/24 06:00
MHDA- 2010/10/23 06:00
CRDT- 2010/04/24 06:00
PHST- 2010/04/24 06:00 [entrez]
PHST- 2010/04/24 06:00 [pubmed]
PHST- 2010/10/23 06:00 [medline]
AID - TRF2644 [pii]
AID - 10.1111/j.1537-2995.2010.02644.x [doi]
PST - ppublish
SO  - Transfusion. 2010 Aug;50(8):1690-701. doi: 10.1111/j.1537-2995.2010.02644.x. Epub 
      2010 Apr 15.