Immune potential of allogeneic equine induced pluripotent stem cells.

This research article explores the immune response elicited by induced pluripotent stem cells (iPSC) in horses. The study examines the degree to which these cells express specific immune markers and how the horse organism responds to them when injected under the skin.

Introduction

• Induced pluripotent stem cells (iPSC) have significant implications in cellular therapy and regenerative medicine. They are cells that have been reprogrammed back into a state of pluripotency, being able to differentiate into any cell type in the body. This characteristic makes them a potential candidate for cell replacement therapies.
• The main obstacle in using iPSC for treatment is their antigenicity, or their ability to stimulate an immune response, which could lead to rejection of these cells by the recipient’s immune system. This is often linked to the expression of major histocompatibility complex (MHC) molecules, proteins that help the immune system recognize foreign substances.
• Previous studies have shown that iPSC derived from humans and mice have lower levels of MHC expression, suggesting they may be safe for use in transplantation. This study aims to investigate if the same is true for iPSC derived from horses (eiPSC).

Methods

• The researchers generated two lines of green fluorescent protein-expressing eiPSC and examined them using flow cytometry to assess MHC expression.
• One of the cell lines was then injectected intradermally (between the layers of the skin) into two unrelated experimental horses. The researchers gathered blood samples before and after transplantation and tracked any immune response.
• They also performed histopathological and immunofluorescent analyses on tissue samples from the injected areas at different points after the transplantation.

Results

• The researchers found that both eiPSC lines weakly expressed MHC molecules.
• Seven days after the transplantation, the horses did not exhibit any obvious systemic response, suggesting that the eiPSC were not rejected.
• However, the injections caused a small reaction at the skin level, and the researchers found CD4+ and CD8+ mononuclear cells (two types of immune cells) in the skin sections even 30 days after transplantation, indicating a moderate cellular response.

Conclusion

• The researchers conclude that transplantation of allogeneic eiPSC in horses triggers a moderate immune response but not an acute rejection. This suggests that using iPSC from a genetically different individual (allogeneic transplantation) could be feasible for regenerative medicine applications.
• The initial findings suggest that it might be worth exploring the creation of an eiPSC bank for future use in regenerative medicine.