Bet Cell Therapy in Diabetes Type 1

Inclusion Criteria: Group A: Patients with loss of long-term function after intraportal implantation (- Patients with type 1 insulin-dependent diabetes who received two intraportal implantations \> 12 months ago. * Random C-peptide between 0.09 and 0.5 ng/dl (glycemia between 100 and 200 mg/dl) * Cooperative and reliable patient giving informed consent by signature Group B: Patients that are candidates for islet cell transplantation - age 18-65 years, male or female, Caucasian or not; only subjects \< 50 yrs will be allocated to the rituximab treatment arm * body weight \< 100 kg; patients with a bodyweight of \< 80kg, will receive priority * patients with a BMI ≤ 27 kg/m2 will receive priority * Type 1 insulin-dependent diabetes * C-peptide \< 0.07 nmol/l (\< 0.2 µg/l) 6 min. after glucagon IV (1mg) (glycemia \> 180 mg/dl) * Intensive insulin therapy for more than two years, patients with insulin pump during at least 2 months before inclusion will receive priority * Patients should have at least one of the following chronic complications of diabetes: * albuminuria 30-1000mg/ 24hrs on 3 separate determinations (\>1 month) outside an episode of illness, despite intake of ACE inhibitors; mean systolic blood pressure should be under 130 mmHg and mean diastolic blood pressure under 85 mmHg, when measured at home with ambulatory BP monitoring * moderate or severe non-proliferative or proliferative retinopathy * hypoglycemic unawareness * Cooperative and reliable patient giving informed consent by signature Exclusion Criteria: * Women of reproductive age * Smoker * EBV antibody negativity * HIV 1 \& 2 antibody positivity * CMV IgM positivity * Hepatitis B infection * GFR \< 45 ml/min/1.72 m2 * Albuminuria ≥ 1000 mg/24 hrs * History of thrombosis or pulmonary embolism * History of malignancy, tuberculosis or chronic viral hepatitis * History of any other serious illness which could be relevant for the protocol * Presence of clinical significant HLA antibodies * Blood donation within one month prior to screening * Symptoms and/or signs of infection, particularly (present or past) endocarditis, osteomyelitis * Any history of hepatic or neoplastic disease * Any history of renal disease (except diabetes) * Abnormal liver function tests and/or NMR of liver * Hemoglobinopathy * History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risks to the patient * Use of illicit drugs or overconsumption of alcohol (\> 3 IU/day) or history of drug or alcohol abuse * Being legally incapacitated, having significant emotional problems at the time of the study, or having a history of a psychiatric disorder that may be exacerbated by the transplantation procedure or interfere with compliance during follow-up * Having received antidepressant medications during the last 6 months * Participating in another pharmacological study