Clinical islet transplantation Stephanie A Amiel, BSc, MD, FRCP RD Lawrence Professor of Diabetic Medicine Kings College London School of Medicine Diabetes Research Group

Treatment of organ failure? Renal failure Liver failure Heart failure Islet failure Kidney transplant Liver transplant Heart transplant INSU U100

Case Histories 1.Born 1944; T1DM 1966; keen runner 2.Born 1965; T1DM 1987; HCA on locked ward 3.Born 1985; T1DM 1994; mother of two afraid to be in charge of my granddaughter threatened with medical redundancy you just drove across a red light, Mummy

GLUCOSE-RESPONSIVE INSULIN DELIVERY Bionics vs nature?

Nature – whole pancreas or islets?

Islet Transplantation 1998 established laboratory 2000 proof of concept st UK patient 2008 NCG funded programme

Insulin Independence, Insulin Dependence, Graft failure *C-peptide data not available at Day 75 **Year 3 status independent of re-infusion CITR Islet Alone Recipients outcome From all infusions

CITR 2007 SEVERE HYPOGLYCEMIA FOLLOWING LAST TRANSPLANT

1 person with 4% reduction in HbA1c 2 people back in work 1 woman resumed running and babysitting her grandchildren 2 children safely back on school run 3 people achieved insulin independence Clinical Outcomes: Diabetes UK patients

UK ITC Shaw, Manus, Amiel, Huang NCG: April isolation centres 6 Transplant centres Intractable hypoglycaemia Islet after kidney Local and remote

Problems to be solved Current Organ supply/distribution Sub-optimal immunosuppression Research Prevent loss of islets on administration Improve immunosuppression Make new islets to give greater loads and re- transplant if required

Meanwhile Whatever cell therapy we devise, it will need to be safer than insulin therapy For a small number of patients, it already is