Samenvatting
Background
Intraportal injection of pancreatic islets in type 1 diabetes patients results in functional beta cell implants which can improve metabolic control and restore hypoglycemic awareness (1,2). Implant function declines over time (3) but little information exists on the underlying process. We examined in vivo and in situ correlations for omentum implants, first in rodents (4) and then in patients. Two cases of an implant in the omentum have been reported so far (5,6).
Methods
Seven patients participated in a pilot study in which outcome of an omentum implant was monitored over three months, and followed, in case of absent metabolic effect, by an intraportal implant at which time an omental biopsy was taken. Omental access occurred under laparoscopy without adverse events. All recipients were under immune suppression (induction ATG, maintenance MMF/tacrolimus).
Results
Omental implants resulted in a lower functional beta cell mass than intraportal implants. Histological analysis showed small endocrine cell aggregates, containing insulin- and glucagon-positive cells, with adjacent endothelial cells, lymphocyte clusters and sometimes ductal structures. A prior omentum implant did not negatively influence outcome of an intraportal implant compared to intraportal alone recipients (n=10): no differences at 6 and 12 months post-transplantation in hyperglycemic clamp values, BETA-2 score, HbA1c, insulin dose and glycemic variability.
Conclusions
A pancreatic islet cell implant in the omentum establishes functioning beta cells in type 1 diabetes patients but their metabolic outcome was lower than for intraportal implants. It allowed histopathologic analysis of the implant and did not interfere with outcome of a subsequent intraportal implant.
(1) Keymeulen et al. Proc Natl Acad Sci USA 2006. (2) Shapiro et al. N Engl J Med 2000. (3) Ryan et al. Diabetes 2005. (4) Jacobs-TulleneersThevissen et al. Diabetologia 2010.(5) Baidal et al. N Engl J Med 2017. (6) Schmidt. Nat Biotechnol 2017
Intraportal injection of pancreatic islets in type 1 diabetes patients results in functional beta cell implants which can improve metabolic control and restore hypoglycemic awareness (1,2). Implant function declines over time (3) but little information exists on the underlying process. We examined in vivo and in situ correlations for omentum implants, first in rodents (4) and then in patients. Two cases of an implant in the omentum have been reported so far (5,6).
Methods
Seven patients participated in a pilot study in which outcome of an omentum implant was monitored over three months, and followed, in case of absent metabolic effect, by an intraportal implant at which time an omental biopsy was taken. Omental access occurred under laparoscopy without adverse events. All recipients were under immune suppression (induction ATG, maintenance MMF/tacrolimus).
Results
Omental implants resulted in a lower functional beta cell mass than intraportal implants. Histological analysis showed small endocrine cell aggregates, containing insulin- and glucagon-positive cells, with adjacent endothelial cells, lymphocyte clusters and sometimes ductal structures. A prior omentum implant did not negatively influence outcome of an intraportal implant compared to intraportal alone recipients (n=10): no differences at 6 and 12 months post-transplantation in hyperglycemic clamp values, BETA-2 score, HbA1c, insulin dose and glycemic variability.
Conclusions
A pancreatic islet cell implant in the omentum establishes functioning beta cells in type 1 diabetes patients but their metabolic outcome was lower than for intraportal implants. It allowed histopathologic analysis of the implant and did not interfere with outcome of a subsequent intraportal implant.
(1) Keymeulen et al. Proc Natl Acad Sci USA 2006. (2) Shapiro et al. N Engl J Med 2000. (3) Ryan et al. Diabetes 2005. (4) Jacobs-TulleneersThevissen et al. Diabetologia 2010.(5) Baidal et al. N Engl J Med 2017. (6) Schmidt. Nat Biotechnol 2017
| Originele taal-2 | English |
|---|---|
| Status | Published - 14 mrt. 2019 |
| Evenement | Belgian Transplantation Society - Antwerp, Belgium Duur: 14 mrt. 2019 → 14 mrt. 2019 |
Conference
| Conference | Belgian Transplantation Society |
|---|---|
| Land/Regio | Belgium |
| Stad | Antwerp |
| Periode | 14/03/19 → 14/03/19 |