Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. C URRENT O PINION Mesenchymal stromal cells as a means of controlling pathological T-cell responses in allogeneic islet transplantation James L. Reading a , Shereen Sabbah a , Sarah Busch b , and Timothy I.M. Tree a Purpose of review To evaluate the potential for mesenchymal stromal cells (MSCs) to regulate T-cell responses responsible for graft destruction following allogeneic islet transplantation (AIT). Recent findings Despite a high level of primary graft function being observed in most individuals following AIT, the majority of recipients require exogenous insulin within 5 years, presumably due to graft attrition. Although this process is not fully understood, recent evidence suggests that a combination of chronic allograft rejection and/or the recrudescence of anti-islet autoimmunity govern islet loss. Emerging reports highlight that the pathology of AIT may involve the proliferation, effector function and homeostatic expansion of alloreactive and autoreactive T-cell pools. MSCs exhibit several desirable characteristics, which may advocate their use in AIT. This includes the capacity to suppress alloreactive and autoimmune T-cell responses, and promote a cytokine environment that is likely to be graft protective. However, further work is needed to clarify if MSCs can function in the setting of immune suppression and discern how they may effect T-cell effector functions and influence homeostatic expansion. Summary MSCs exhibit the potential to regulate the T-cell-driven processes that underlie disease pathology in AIT, but further study may be required to maximize their therapeutic efficacy. Keywords allogeneic islet transplantation, MSC, T cell, T1D INTRODUCTION Research over the past 35–40 years has demonstrated that type 1 diabetes mellitus (T1D) is a T-cell-medi- ated autoimmune disease in which the destruction of insulin secreting b-cells is driven by islet-specific T cells; leading to loss of insulin production and glycemic control [1]. The administration of exogen- ous insulin is unable to completely mimic physio- logic insulin secretion and, combined with the failure of glucose counter-regulation, increases the risk of severe hypoglycemia, and secondary vascular com- plications. Allogeneic islet transplantation (AIT) can pro- vide long-term improvements in glycemic control, enhancing the overall quality of life in the majority of recipients. However, the shortage of donor organs, high cost of islet isolation and the require- ment for life-long immunosuppression means this procedure is currently reserved for a select group of T1D patients with negative fasting C-peptide (<0.3 ng/ml), severe glycemic lability, hypoglyce- mia unawareness and consistently elevated HbA 1c levels (>8%) [2,3]. The success rate of islet transplantation was improved significantly by the introduction of the Edmonton protocol in 2000. This landmark trial demonstrated the successful reversal of T1D in all seven patients using a glucocorticoid-free immuno- suppressive regimen at 1 year [4]. However, the 5-year follow-up of this cohort revealed eventual loss of b-cell function and recurrence of diabetes, a Department of Immunobiology, King’s College London, Guy’s Hospital, London, UK and b Athersys, Inc., Cleveland, Ohio, USA Correspondence to Dr Timothy Tree, Department of Immunobiology, King’s College London, 3rd Floor, Borough Wing, Guy’s Hospital, London SE1 9RT, UK. Tel: +44 207 188 1182; e-mail: Timothy.Tree @kcl.ac.uk Curr Opin Organ Transplant 2013, 18:59–64 DOI:10.1097/MOT.0b013e32835c2adf 1087-2418 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-transplantation.com REVIEW