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IN VITRO CELLULAR CO-CULTURE METHOD TO INDUCE IMMUNOLOGICAL TOLERANCE

Immunotherapylymphocyte

Introduction

Autoimmune disorders (AD) affect 5%-10% of the population, significantly decreasing the life expectancy of patients and worsening their quality of life. AD occurs when the immune system fails to self-recognize. In this context, lymphocytes mediate important pro- and anti-inflammatory effects through release of several cytokines. Our invention defines an in vitro method able to modulate the inappropriate activation of autoreactive T-lymphocytes. Thanks to a stem cell mediated process, re-education in recognition of self-antigen of the patient peripheral lymphocytes is achieved and a tolerogenic environment is generated, even in an inflammatory background.

Technical features

The method is based on the creation of an “in vitro artificial thymus” with the co-culture of lymphocytes with heterologous or autologous fibroblast-like limbal stem cells (f-LSCs, mesenchymal stem cells from the corneal stem cell niche). The co-culture system is optimized to require an exiguous number of stem cells with respect to lymphocytes obtained from AD patients (1:100). After the re-education process “smart immunomodulation” is obtained: the f-LSCs, induced by Th1 pro-inflammatory cytokines released by peripheral lymphocytes, improve their expression for several immune regulatory factors hindering clonal Th1 cell expansion and driving Th17 differentiation in favor of Th2 cells.

Possible Applications

  • In translational medicine as an in vitro auto-immune disease study model;
    • A protocol for immuno-therapy purpose;
    • Treatment of rejection in organ transplantation.

Advantages

  • Safe administration in humans: f-LSCs are immunologically privileged as they do not express the complete pattern of molecules to fully activate T-lymphocytes, (class II HLA) and maintain stem features after culture;
  • Production is simple and economically advantageous;
  • f-LSCs exert immunomodoulation acting as stem cell educators of autoimmune T lymphocytes.