title: Immune properties of human umbilical cord Wharton's jelly-derived cells.
abstract: Cells isolated from Wharton's jelly, referred to as umbilical cord matrix stromal (UCMS) cells, adhere to a tissue-culture plastic substrate, express mesenchymal stromal cell (MSC) surface markers, self-renew, and are multipotent (differentiate into bone, fat, cartilage, etc.) in vitro. These properties support the notion that UCMS cells are a member of the MSC family. Here, the immune properties of UCMS cells are characterized in vitro. The overall hypothesis is that UCMS cells possess immune properties that would be permissive to allogeneic transplantation. For example, UCMS cells will suppress of the proliferation of "stimulated" lymphocytes (immune suppression) and have reduced immunogenicity (e.g., would be poor stimulators of allogeneic lymphocyte proliferation). Hypothesis testing was as follows: first, the effect on proliferation of coculture of mitotically inactivated human UCMS cells with concanavalin-A-stimulated rat splenocytes was assessed in three different assays. Second, the effect of human UCMS cells on one-way and two-way mixed lymphocyte reaction (MLR) assays was determined. Third, the expression of human leukocyte antigen (HLA)-G was examined in human UCMS cells using reverse transcription-polymerase chain reaction, since HLA-G expression conveys immune regulatory properties at the maternal-fetal interface. Fourth, the expression of CD40, CD80, and CD86 was determined by flow cytometry. Fifth, the cytokine expression of UCMS cells was evaluated by focused gene array. The results indicate that human UCMS cells inhibit splenocyte proliferation response to concanavalin A stimulation, that they do not stimulate T-cell proliferation in a one-way MLR, and that they inhibit the proliferation of stimulated T cells in a two-way MLR. Human UCMS cells do not inhibit nonstimulated splenocyte proliferation, suggesting specificity of the response. UCMS cells express mRNA for pan-HLA-G. UCMS cells do not express the costimulatory surface antigens CD40, CD80, and CD86. UCMS cells express vascular endothelial growth factor and interleukin-6, molecules previously implicated in the immune modulation observed in MSCs. In addition, the array data indicate that UCMS cells make a cytokine and other factors that may support hematopoiesis. Together, these results support previous observations made following xenotransplantation; for example, there was no evidence of frank immune rejection of undifferentiated UCMS cells. The results suggest that human UCMS will be tolerated in allogeneic transplantation. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506, USA. weiss@vet.ksu.edu
authors.forename: Mark L
authors.initials: ML
authors.lastname: Weiss
authors.forename: Cameron
authors.initials: C
authors.lastname: Anderson
authors.forename: Satish
authors.initials: S
authors.lastname: Medicetty
authors.forename: Kiran B
authors.initials: KB
authors.lastname: Seshareddy
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Weiss
authors.forename: Irene
authors.initials: I
authors.lastname: VanderWerff
authors.forename: Deryl
authors.initials: D
authors.lastname: Troyer
authors.forename: Kevin R
authors.initials: KR
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006680:HLA Antigens / Q000096:biosynthesis / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D003208:Concanavalin A