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AG Figueiredo

Cellular Therapy

   Institut für Transfusionsmedizin

   Medizinische Hochschule Hannover

   Feodor-Lynen-Straße 5

   30625 Hannover

   Tel.: +49 (511) 532 9711

   Fax: +49 (511) 532 9701


Figure 1: HLA-silenced megakaryocytes and proplatelets derived from CD34+ progenitor cells.
Figure 2: HLA-silenced endothelial cells

   Our research work focuses the reduction of the immunogenicity of cells

   or tissues to prevent rejection after allogeneic transplantation.

   Despite the recent improvements in improving HLA matching in

   transplantation, HLA class I and class II disparities remain a major

   obstacle in allogeneic transplantation. Previously, we have shown the feasibility    to knockdown the expression of HLA class I and HLA-class II

   molecules in several cell types such as monocytes and B-cells using

   short hairpins RNAs delivered by lentiviral vectors.

   In in vitro and in vivo models, we showed that MHC class I silenced cells

   efficiently abrogate or escape the immune response contributing for an    increased graft survival after transplantation in an allogeneic setting.

   Also, we have silenced the expression of HLA class I molecules in CD34+

   progenitor cells and differentiated them into HLA-deficient platelets

   (Figure 1). Since platelets are anucleated cells, they do not loose

   their main biologic function after irradiation and, therefore, safety

   concerns related to gene transfer are reduced. Therefore, this strategy

   has a high potential to be rapidly applied in clinical approaches

   to treat platelet refractoriness observed due to immune responses

   against HLA. Another aim our team is the generation of an HLA universal    endothelium. Therefore, we silenced the expression of HLA class I and

   class II molecules directly in tissues such as corneas or in endothelial

   cells that might be used for transplantation or re-cellularization

   in vascular therapeutics.