title: Hair follicle dermal sheath derived cells improve islet allograft survival without systemic immunosuppression.
abstract: Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation.
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of British Columbia, 950 West 10th Avenue, Vancouver, BC, Canada V5Z 1M9.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Gigi
authors.initials: G
authors.lastname: Leung
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Trisia
authors.initials: T
authors.lastname: Breitkopf
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Eddy
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of British Columbia, 950 West 10th Avenue, Vancouver, BC, Canada V5Z 1M9.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kwong
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Noushin
authors.initials: N
authors.lastname: Akhoundsadegh
authors.affiliation: Department of Surgery, University of British Columbia, 950 West 10th Avenue, Vancouver, BC, Canada V5Z 1M9.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Warnock
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Jerry
authors.initials: J
authors.lastname: Shapiro
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada V5Z 4E3.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McElwee
mesh_terms: D064591:Allografts / Q000276:immunology*; D000818:Animals; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000601:surgery; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D018859:Hair Follicle / Q000166:cytology*; D007108:Immune Tolerance / Q000276:immunology; D007165:Immunosuppression Therapy; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology