Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device

Area of Science:

• Biomaterials Science
• Immunology
• Cardiovascular Engineering

Background:

• Left ventricular assist devices (LVADs) require anticoagulative therapy due to poor hemocompatibility of their surfaces.
• Endothelial cell (EC) seeding enhances hemocompatibility, but autologous EC availability is limited.
• Allogeneic ECs are abundant but trigger immune responses due to human leukocyte antigen (HLA) disparities, leading to EC loss.

Purpose of the Study:

• To investigate the use of allogeneic, low-immunogenic ECs for endothelializing LVAD sintered inflow cannulas (SICs).
• To reduce EC immunogenicity by silencing HLA class I expression using short-hairpin RNA delivered via a lentiviral vector.

Main Methods:

• Conditional silencing of HLA class I expression on ECs by up to 70% using an inducible lentiviral vector.
• Assessing endothelialization rates, cell proliferation, phenotypic markers, thrombogenicity, and immune response to HLA-silenced ECs on SICs.
• Evaluating cell lysis rates of HLA-silenced ECs against allogeneic T cells and anti-HLA antibodies.

Main Results:

• Comparable endothelialization rates were achieved with both HLA-expressing and HLA-silenced ECs.
• Silencing HLA expression did not impair EC proliferation, phenotypic markers, or cytokine secretion.
• HLA-silenced EC-coated SICs demonstrated reduced thrombogenicity and lower cell lysis when exposed to allogeneic immune components.

Conclusions:

• Allogeneic, HLA-silenced ECs offer a promising strategy for LVAD endothelialization.
• This approach could mitigate immune responses, reduce reliance on anticoagulative therapy, and improve LVAD safety.
• Genetically modified ECs represent a potential advancement in reducing LVAD-associated complications.