Abstract
BackgroundAlopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens.MethodsWe have developed a Stem Cell Educator therapy in which a patient’s blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the “educated” autologous cells to the patient’s circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years).ResultsClinical 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.ConclusionsCurrent clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA.Trial registrationClinicalTrials.gov, NCT01673789, 21 August 2012
Highlights
Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss
The peripheral blood-derived mononuclear cells (PBMCs) were stimulated for 5 days with Dynabeads coupled with anti-CD3, anti-CD28, and anti-CD137 antibodies (Life Technologies, Grand Island, NY, USA) in the presence of 50 U/ml recombinant human IL-2 and 5 ng/ml recombinant human IL-7 (R&D Systems, Minneapolis, MN), and incubated at 37°C, in 8% CO2
Suppressed proliferation of antigen-specific T cells by co-culture with cord blood-derived multipotent stem cells (CB-SC) The expansion of antigen-specific autoreactive T cells is the critical step leading to the destruction of tissues in autoimmune diseases
Summary
Alopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Li et al BMC Medicine (2015) 13:87 current management of AA This clinical approach should address multiple or all of the underlying causes of autoimmunity in AA. Similar to all other autoimmune diseases, possible triggers for autoimmunity in AA include genetic, epigenetic, physical, emotional, social, and environmental factors. These complicated factors may act independently or jointly to break down the “immune privilege” of hair follicles through different molecular and cellular mechanisms, resulting in the autoimmune destruction of hair follicles by multiple immune cells, such as CD4+ and/or CD8+ T cells and natural killer (NK) cells [1,4,5,6,7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
