Institut für Transfusionsmedizin
Medizinische Hochschule Hannover
Tel.: +49 (511) 532 9711
Fax: +49 (511) 532 9701
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.