Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression

Abstract

Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 AE 9.2 years, duration of diabetes 35 AE 9 years) received a total of 22 islet transplantations. One-and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 AE 13.1 (7.4 AE 1.2%) to 44.5 AE 11.8 mmol/molHb (6.2 AE 0.9%) (p ¼ 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control.

Clinical-Grade Isolated Human Kidney Perivascular Stromal Cells as an Organotypic Cell Source for Kidney Regenerative Medicine

“…In order to evaluate whether hkPSCs are a potential new cell source for use in cell therapy to treat kidney disease in a clinical setting, we chose to develop a clinical‐grade acceptable SOP with the use of clinical‐grade materials and enzymes. This protocol is developed on the basis of the pancreatic islet isolation protocol currently in use for clinical application in our center . Perivascular stromal cells were isolated on the basis of NG2 expression.…”

Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

“…β Cell replacement therapy is an attractive therapy to achieve normoglycemia in patients with diabetes mellitus due to severe β cell failure ( Nijhoff et al., 2016 , Ricordi et al., 1989 ). The shortage of organ donors severely limits the number of patients that are eligible for current β cell replacement therapy, i.e., pancreas or islet transplantation.…”

A Novel Clinical Grade Isolation Method for Human Kidney Perivascular Stromal Cells

“…Here we show a novel isolation method of human kPSCs for whole organs based on perfusion with clinical grade enzymes and materials. The protocol is adapted from the clinical islets of Langerhans isolation protocol currently in use for clinical application in our center 18 .…”