title: Hair regrowth in alopecia areata patients following Stem Cell Educator therapy.
abstract: BACKGROUND
  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. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens.
  
  
  METHODS
  We 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Current 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.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01673789, 21 August 2012.
authors.affiliation: Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, P.R. China. Liyanjia2008@gmail.com.
authors.forename: Yanjia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cell Therapy Center, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, P.R. China. info@tianhecell.com.
authors.forename: Baoyong
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Dermatology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, P.R. China. Hepeng_wang@yahoo.com.
authors.forename: Hepeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Jinan Central Hospital, Shandong University, Jinan, Shandong, 250013, P.R. China. Hengli59@yahoo.com.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: Cell Therapy Center, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, P.R. China. Quanhai_li@yahoo.com.
authors.forename: Quanhai
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, Jinan Central Hospital, Shandong University, Jinan, Shandong, 250013, P.R. China. Zhaodong17@yahoo.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics, Jinan Central Hospital, Shandong University, Jinan, Shandong, 250013, P.R. China. Chenyana55@yahoo.com.
authors.forename: Yana
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tianhe Stem Cell Biotechnologies Inc., Jinan, Shandong, 250055, P.R. China. Zhang.ye89@yahoo.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianhe Stem Cell Biotechnologies Inc., Jinan, Shandong, 250055, P.R. China. zhao@tianhecell.com.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Li
authors.affiliation: Cell Therapy Center, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, P.R. China. Jun.zhang70@yahoo.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tianhe Stem Cell Biotechnologies Inc., Jinan, Shandong, 250055, P.R. China. shanfenwang@yahoo.com.
authors.forename: Shanfeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Tianhe Stem Cell Biotechnologies Inc., Jinan, Shandong, 250055, P.R. China. Jieshen20@yahoo.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Tianhe Stem Cell Biotechnologies Inc., Jinan, Shandong, 250055, P.R. China. Yunxiangli6@gmail.com.
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: CORD:USE Cord Blood Bank, Orlando, FL, 32810, USA. eguindi@corduse.com.
authors.forename: Edward
authors.initials: E
authors.lastname: Guindi
authors.affiliation: Tianhe Stem Cell Biotechnologies Inc., Jinan, Shandong, 250055, P.R. China. yzhao@hackensackUMC.org.|Department of Research, Hackensack University Medical Center, 40 Prospect Avenue, Hackensack, NJ, 07601, USA. yzhao@hackensackUMC.org.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000506:Alopecia Areata / Q000276:immunology* / Q000628:therapy*; D018920:Coculture Techniques; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D039902:Multipotent Stem Cells / Q000276:immunology*; D011788:Quality of Life; D015854:Up-Regulation; D055815:Young Adult