Human iPSC-Derived Endothelial Cells Exhibit Reduced Immunogenicity in Comparison With Human Primary Endothelial...

Area of Science:

• Stem Cell Biology
• Immunology
• Vascular Biology
• Regenerative Medicine

Background:

• Human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) offer potential for treating ischemic vascular diseases.
• Clinical application is hindered by safety concerns, particularly aberrant immunogenicity from the reprogramming process.

Purpose of the Study:

• To investigate the immunological phenotypes of iPSC-ECs.
• To compare iPSC-ECs side-by-side with primary human umbilical vein ECs (HUVECs) regarding immune protein expression and immune cell response.

Main Methods:

• Examined surface protein expression (MHC Class I/II, ICAM-1, E-selectin, VCAM-1) on iPSC-ECs and HUVECs under resting and cytokine-activated conditions.
• Monitored proliferation of human peripheral blood mononuclear cells (PBMCs) co-cultured with iPSC-ECs versus HUVECs over 5 days.
• Conducted mixed lymphocyte reactions (MLR) to assess T-cell proliferation and measured proinflammatory cytokine secretion.

Main Results:

• iPSC-ECs showed similar MHC Class I and ICAM-1 expression to HUVECs but differential TNF-α-induced E-selectin and VCAM-1 expression.
• iPSC-ECs induced decreased PBMC proliferation and T-cell activation in alloreactivity and IFN-γ-stimulated conditions compared to HUVECs.
• Co-cultures with iPSC-ECs secreted lower levels of proinflammatory cytokines than HUVEC co-cultures.

Conclusions:

• iPSC-ECs exhibit a generally weaker inflammatory immune response compared to primary ECs.
• This suggests potential hypoimmunogenicity, indicating a reduced risk of immune rejection in transplant settings.
• Findings support the safe and effective use of iPSC-ECs in cell therapies for vascular diseases.