title: Human umbilical cord-derived mesenchymal stem cells suppress proliferation of PHA-activated lymphocytes in vitro by inducing CD4(+)CD25(high)CD45RA(+) regulatory T cell production and modulating cytokine secretion.
abstract: Bone marrow-derived mesenchymal stem cells (MSCs) are promising candidate cells for therapeutic application in autoimmune diseases due to their immunomodulatory properties. Unused human umbilical cords (UC) offer an abundant and noninvasive source of MSCs without ethical issues and are emerging as a valuable alternative to bone marrow tissue for producing MSCs. We thus investigated the immunomodulation effect of umbilical cord-derived MSCs (UC-MSCs) on human peripheral blood mononuclear cells (PBMCs), T cells in particular, in a co-culture system. We found that UC-MSCs efficiently suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated PBMCs (p<0.01). Kinetic analysis revealed that UC-MSCs primarily inhibited the division of generation 3 (G3) and 4 (G4) of PBMCs. In addition, UC-MSCs augmented the expression of CD127(+) and CD45RA(+) but reduced the expression of CD25(+) in PBMCs stimulated by PHA (p<0.05). Furthermore, UC-MSCs inhibited PHA-resulted increase in the frequency of CD4(+)CD25(+)CD127(low/-) Tregs significantly (p<0.01) but augmented PHA-resulted increase in the frequency of CD4(+)CD25(high)CD45RA(+) Tregs to about three times in PBMCs. The levels of anti-inflammatory cytokines, PEG2, TGF-β, and IL-10 were greatly up-regulated, accompanied by a significant down-regulation of pro-inflammatory IFN-γ in the co-culture (p<0.01). Our results showed that UC-MSCs are able to suppress mitogen-induced PBMC activation and proliferation in vitro by altering T lymphocyte phenotypes, increasing the frequency of CD4(+)CD25(high)CD45RA(+) Tregs, and modulating the associated cytokine production. Further studies are warranted to investigate the therapeutic potential of UC-MSCs in immunologically-diseased conditions.
authors.affiliation: Department of Critical Care Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong 250012, China; The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA.
authors.forename: Hongna
authors.initials: H
authors.lastname: Yang
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Sun
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anatomy, Capital Medical University, Beijing 100069, China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Duan
authors.affiliation: Department of Neurology, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, China. Electronic address: bjz@sdu.edu.cn.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Bi
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA. Electronic address: tqu@uic.edu.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Qu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015704:CD4 Antigens; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D010835:Phytohemagglutinins; D017493:Leukocyte Common Antigens
keywords: Immunosuppressive function; Soluble cytokines; Tregs; UC-MSCs