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.
Highlights
Transplantation of pancreatic islets is potentially a curative treatment for type 1 diabetes
We proposed to use cultured hair follicle (HF) derived immune privilege (IP) cells to protect islet allograft survival
We first examined IP-related gene expression in dermal sheath cup cells (DSCC), dermal papilla (DP), and dermal sheath (DS) cells cultured for 4 passages, relative to FB, by qPCR (Figure 1(a))
Summary
Transplantation of pancreatic islets is potentially a curative treatment for type 1 diabetes. The systemic immunosuppressive drugs that recipients must use lifelong to prevent rejection of the islet allografts suppress immunity to other antigens, thereby increasing the risk of opportunistic infections and cancers [1,2,3]. These drugs have an adverse impact on the transplanted islets’ survival, causing the function of islets to decline over time, such that many recipients must eventually resume insulin injections for control of blood glucose levels [1,2,3]. Cotransplantation of either amniotic epithelial cells or Sertoli cells sustains islet allograft survival, without systemic immunosuppression, suggesting that a more physiological approach to immune protection of transplanted islets can be achieved. We examined the effects of cultured DSCC on beta cell survival in a mouse islet transplantation model
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