# Immunogenicity of induced pluripotent stem cell-derived smooth muscle cells results from a reduction in the expression of indoleamine 2,3 dioxygenase (IDO-1)

## TL;DR

Stem cell-derived smooth muscle cells are more immunogenic than natural ones due to lower IDO-1 activity, which could impact their use in therapies.

## Contribution

The study reveals that reduced IDO-1 expression in iPSC-derived smooth muscle cells leads to increased immunogenicity compared to natural cells.

## Key findings

- iPSC-derived smooth muscle cells trigger T cell proliferation unlike natural vascular smooth muscle cells.
- IDO-1 expression and function are significantly reduced in iPSC-derived smooth muscle cells.
- iPSC-derived cells fail to modulate immune responses in co-culture with activated PBMCs.

## Abstract

Smooth muscle cells (SMCs) derived from allogeneic induced pluripotent stem cells (iPSC) hold significant potential in cellular therapy for many cardiovascular diseases. However, their immunological profile is poorly characterized, limiting their clinical progression.

This study aimed to investigate the immunogenicity of iPSC-SMC in comparison with naturally derived vascular SMCs (v-SMCs).

We found iPSC-SMCs, in contrast to naturally derived vascular SMCs (v-SMC), triggered T effector memory (TEM) cell proliferation. However, expression of TEM activation-related proteins was comparable between both cell types. Since arterial v-SMCs can also establish immunoprivilege through indoleamine 2,3 dioxygenase (IDO-1) activity, we therefore investigated IDO-1 expression in two independently engineered iPSC-SMCs (NIBSC 8 (N8) and Yale 6 (Y6)). IDO-1 expression and functionality was markedly reduced in both iPSC-SMC lines compared to v-SMC and unlike v-SMC, neither iPSC-SMC line could modulate the immune response in a co-culture with CD3/CD28 activated peripheral blood mononuclear cells (PBMC).

These results indicate that iPSC-SMC’s impaired ability to modulate the immune response through IDO-1 expression contributes to their differing immunogenicity to v-SMC and highlights the importance of immune phenotyping for therapeutic applications of iPSC-derivatives.