title: Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture - a preliminary study.
abstract: The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the co-cultures. Our results showed that UC-MSCs significantly increased the frequency of CD4+CD25+CD127low/- Tregs in resting CD4+ T cells (p<0.01) from MS, accompanied by the significantly augmented production of cytokine prostaglandin E2, transforming growth factor (-β1, and interleukin-10, along with a reduced interferon-γ production in these co-cultures (p<0.05 - 0.01). More importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the proliferation of PHA-stimulated autologous and allogeneic CD4+CD25- T effector cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC-primed (naïve) Tregs from the same MS patients (p<0.01). Furthermore, no remarkable differences in suppressing the proliferation of PHA-stimulated CD4+CD25- Teffs was observed in UC-MSC-primed Tregs from MS patients and naïve Tregs from healthy subjects. The impaired suppressive function of Tregs from MS can be completely reversed in a co-culture by UC-MSC modulation. This report is the first to demonstrate that functional defects of Tregs in MS can be repaired in vitro using a simple UC-MSC priming approach.
authors.affiliation: Department of Critical-Care Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.|Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Hongna
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.|R & D, Cell and Tissue Bank of Shandong Province, Jinan, Shandong, China.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Qu
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D006801:Humans; D056747:Immunomodulation; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
keywords: Immune response; Immunity; Immunology and Microbiology Section; T regulatory cells; immunomodulation; multiple sclerosis; stem cell priming; umbilical cord mesenchymal stem cells