Mechanisms utilized by feline adipose-derived mesenchymal stem cells to inhibit T lymphocyte proliferation
Abstract
Background: Feline adipose-derived mesenchymal stem cells (ASCs) have been successfully used in clinical trials for the treatment of immune-mediated diseases with T cell dysregulation. However, the immunomodulatory pathways utilized by feline ASCs to suppress T cell activation have not been fully determined. We investigated the mechanisms used by feline ASCs to inhibit T cell proliferation, including the soluble factors and the cell-cell contact ligands responsible for ASC-T cell interaction.
Methods: The immunomodulatory activity of feline ASCs was evaluated via cell cycle analysis and in vitro mixed leukocyte reaction using specific immunomodulatory inhibitors. Cell-cell interactions were assessed with static adhesion assays, also with inhibitors.
Results: Feline ASCs decrease T cell proliferation by causing cell cycle arrest in G0-G1. Blocking prostaglandin (PGE2), but not IDO, partially restored lymphocyte proliferation. Although PDL-1 and CD137L are both expressed on activated feline ASCs, only the interaction of intercellular adhesion molecule 1 (ICAM-1, CD54) with its ligand, lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), was responsible for ASC-T cell adhesion. Blocking this interaction reduced cell-cell adhesion and mediator (IFN-γ) secretion and signaling.
Conclusions: Feline ASCs utilize PGE2 and ICAM-1/LFA-1 ligand interaction to inhibit T cell proliferation with a resultant cell cycle arrest in G0-G1. These data further elucidate the mechanisms by which feline ASCs interact with T cells, help define appropriate T cell-mediated disease targets in cats that may be amenable to ASC therapy, and may also inform potential translational models for human diseases.
Keywords: Adipose tissue; Feline; Immunomodulation, soluble mediators, ligands; Mesenchymal stem cell.
Principal Scientist at Gallant
Dr. Nopmanee Taechangam, DVM, PhD, joined Gallant in 2021 and serves as a Principal Scientist specializing in veterinary regenerative medicine and stem cell therapy. A Fulbright scholar, she earned her PhD in Integrative Pathobiology from UC Davis, where her research focused on mesenchymal stem cell therapies for immune-mediated and infectious diseases in animals.
Dr. Taechangam has developed and validated multiple FDA-accepted potency assays for investigational veterinary cell therapies, supporting regulatory approval and product quality standards. Her work focuses on advancing safe, effective, off-the-shelf stem cell therapies for pets at scale.
