A Long-Term Functioning Human Pancreatic Islet Allotransplant

Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus

“…Almost 50 years later, Ballinger and Lacy reported their results isolating and transplanting islets into rats (18). In the late 1970s, various groups including Najarian, Sutherland, et al (19), and Largiader et al (20) described their experience with intraportal and intrasplenic human islet allotransplants in patients with non-autoimmune diabetes, one of which was successful for at least a 10-month follow-up period. In 1990 Scharp et al reported similar success in a patient with T1DM (21); their results were made possible in part by improved islet isolation techniques developed by Ricordi and colleagues (22).…”

Bone marrow as an alternative site for islet transplantation

“…Blood samples were obtained at 0, 1,5,15,20,30, and 60 minutes after injection and were used to determine glucose concentrations. From the IVGTT, the glucose tolerance was quantified from the glucose elimination constant (KG; expressed as percentage of elimination of glucose per minute) as the reduction in circulating glucose between 1 and 15 minutes (KG [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] ) after intravenous administration, following logarithmic transformation of the individual plasma glucose values. 26 A similar estimation was performed for the total 1-to 60-minute glucose disappearance rate (KG ).…”

“…No differences were observed in the euglycemic mice when liver versus bone marrow site was compared for both IVGTT and OGTT parameters. After 1 month, glucose elimination constant between 1 and 15 minutes (KG [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] ) and 1 and 60 minutes (KG 1-60 ) was significantly reduced in intra-BM and intraliver transplanted mice compared with control mice (Figure 4). Subsequently, in mice reaching euglycemia, the KG 1-60 gradually improved in both intra-BM and intraliver models, reaching control values at 3 months after transplantation.…”

“…Subsequently, in mice reaching euglycemia, the KG 1-60 gradually improved in both intra-BM and intraliver models, reaching control values at 3 months after transplantation. The KG [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] in both intra-BM and intraliver also improved, but remained significantly lower than in control mice during all the period of observation. OGTT at 1, 3, 6, and 12 months after transplantation showed that in mice that reached normoglycemia, the AUC for glucose eventually reached that of control mice for islet transplantation in both sites ( Figure 5).…”

“…1 By the 1980s, successful transplantation of islet autografts was reported in humans by using infusion of cells into the patient's liver through the portal venous circulation. [2][3][4] Subsequently, the publication of the first case of insulin independence in a diabetic patient after infusion of islets through the portal vein consecrated the liver as the site of choice for the islet transplantation in humans. 5 The subsequent clinical experience of islet transplantation has been developed almost exclusively using the intrahepatic infusion through the portal vein.…”