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Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue
Skadi Lau1,2, Dorothee Eicke3,4, Marco Carvalho Oliveira3,4
11 Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School , Hannover, Germany .
Tissue Engineering. Part A
|October 6, 2017
Summary
Silencing human leukocyte antigen class I (HLA I) in endothelial cells (EC) reduces immune rejection risk for tissue-engineered vascular grafts. This technique preserves EC function, enabling broader use of allogeneic cells in cardiovascular surgery.
Area of Science:
- Biomedical Engineering
- Cardiovascular Surgery
- Immunology
Background:
- Limited availability of suitable native vessels for hemodialysis shunts and bypass grafts.
- Autologous cells for tissue-engineered vascular grafts (TEVGs) carry low rejection risk but are hard to obtain from elderly patients.
- Umbilical cord blood offers an alternative endothelial cell (EC) source, but allogeneic origin poses rejection risks.
Purpose of the Study:
- To reduce the immunogenic potential of endothelial cells (EC) for TEVG applications.
- To stably silence human leukocyte antigen class I (HLA I) in EC using RNA interference (RNAi).
- To assess the impact of HLA I silencing on EC function and suitability for vascular tissue engineering.
Main Methods:
- Lentiviral vector-mediated RNA interference (RNAi) was used to silence HLA I in EC from peripheral blood, umbilical cord blood, and vein.
- Transduction efficiency and HLA I silencing levels were quantified.
- Endothelial cell surface markers, alignment under flow, LDL uptake, and capillary-like tube formation were analyzed.
- The effect of adipose tissue-derived mesenchymal stem cells on tube formation was evaluated.
Main Results:
- High transduction efficiency (93.1% ± 4.8%) and effective HLA I silencing (up to 67%) were achieved in EC.
- Silenced EC retained expression of key endothelial markers (CD31, VE-cadherin, vWF, eNOS).
- HLA I-silenced EC maintained functional properties, including alignment, LDL uptake, and tube formation, with improved network formation when co-cultured with mesenchymal stem cells.
Conclusions:
- RNAi-mediated silencing of HLA I is a promising strategy to reduce EC immunogenicity.
- This technique preserves essential EC functions required for vascular tissue engineering.
- Enables the use of allogeneic EC sources, expanding cell availability for TEVG generation, especially in urgent clinical situations.
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