Facilitating Cells: A Journey from Bench to Bedside

Abstract

The development of safe conditioning protocols has reduced the morbidity and mortality of hematopoietic stem cell transplantation (HSCT), allowing broader application for treatment of a variety of non-malignant conditions including autoimmune diseases, hemoglobinopathies, metabolic disorders etc., as well as inducing tolerance to solid organ transplants. One of the most successful clinical trials using a facilitating cell enhanced HSCT paired with a kidney transplant has effectively induced tolerance in the absence of immunosuppressive drugs, maintaining the function of the transplanted kidney, and reconstituting the immunocompetence of the recipient. This novel protocol eliminates the need for immunosuppressive drugs, the key source of kidney and liver toxicity, increased malignancy, and shortened life span. CD8+ TCR facilitating cells (FC) are a population of tolerogenic cell which promote hematopoietic stem cell engraftment across human leukocyte antigen (HLA) barriers. In this review, we discuss the bench to bedside journey of FC, from discovery in mouse models, characterization of the subpopulations of FC, the mechanisms by which FC induce tolerance and clinical application. As a novel personalized medicine, FC may change the approach to overcoming HLA barriers for both HSCT and solid organ transplant recipients.