Interactions Between Mesenchymal Stem Cells and T Cells on a Single Cell Level A Nanowell Array

Abstract

Mesenchymal stem cells (MSCs) have been thought to be a potential mode of therapy for immuno-related pathologies, particularly autoimmune diseases. Specifically, the ability to impart immunomodulatory effects on target inflammatory sites makes the use of MSCs particularly attractive for patients affected by taking immunosuppressive medicine, which works to downregulate the immune system on a systemic level. Despite its promises, the interaction between MSCs and T-cells, a key player in the pathophysiology of autoimmune diseases, is not yet well understood, thereby preventing further progress in the clinic. A major obstacle is the highly heterogeneous nature of MSCs in-vitro. Bulk assays commonly carried out discount the inherent heterogeneity, and thus do not provide information with regards to single-cell contributions that may play a critical role in the overall bulk response. To address these issues, we propose to study the single-cell interaction between MSCs and CD4 T cells in a nanowell array. Using the nanowell assay, we demonstrate that individual MSCs appear capable of dynamically modulating the T cell proliferation rate in response to persistent cell-cell interactions in a microenviroment. Based on these results, we anticipate the use of our nanowell assay in the classification of subpopulations within MSCs, ultimately leading to specific therapeutic interventions.