Presented to the AACT 2015 Conference

The complexities of overcoming autoimmunity in Alopecia Areata (AA) are emphasized by the research community’s inability to devise successful treatments with conventional immune therapies, and innovative, comprehensive approaches are needed to find a true cure. Among the challenges, overcoming autoimmune T cell memory is a key hurdle. Physiologically, the human immune system constantly protects the body against a variety of pathogens that may be encountered. Following the recognition and eradication of pathogens through adaptive immune responses, the majority of T cells undergo apoptosis with the remaining cells forming a pool of memory T cells. Increasing evidence demonstrates that autoimmune memory T cells become the “stumbling blocks” and hinder most attempts to treat or cure autoimmune diseases, including AA, type 1 diabetes (T1D), system lupus erythematosus (SLE), multiple sclerosis (MS), and rheumatoid arthritis (RA), among others. Therefore, novel and more comprehensive approaches are needed to fundamentally correct the inordinate dominance of autoimmune T cell memory and overcome the complexities of autoimmune responses. We previously characterized a novel type of stem cell from human cord blood, designated a cord blood-derived multipotent stem cell (CB-SCs). Stem Cell Educator therapy, an approach that uses allogeneic donor-derived CB-SCs, has shown promise in preliminary clinical trials. The therapy involves a closed-loop system that briefly co-cultures the patient’s lymphocytes with adherent CB-SCs in vitro and returns the “educated” lymphocytes (but not the CB-SCs) to the patient’s circulation. In phase 1/2 clinical trials, clinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a “ring of transforming growth factor beta 1 (TGF-β1)” around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β⁺NKG2D⁺ effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs. Thus, Stem Cell Educator therapy functions as “an artificial thymus” that induces the immune tolerance through the action of autoimmune regulator (Aire, expressed in CB-SCs) and restores the immune balance. Stem Cell Educator therapy may hold the potential for a cure for AA and other autoimmune diseases.