Transplantation of fetal porcine pancreas to diabetic or normoglycemic nude mice. Evidence of a rapid engraftment process demonstrated by blood flow and heat shock protein 70 measurements.
Level 5 - mechanism / opinion, no new human data
Animal xenotransplantation model with no human data
PubMed 7604436 · doi:10.1097/00007890-199506270-00004
What was done
Fetal porcine islet-like cell clusters (ICC, approximately 750 clusters / 6 µL volume) were prepared via tissue culture and transplanted under the left kidney capsule of normoglycemic or hyperglycemic C57BL/6J nude mice. Blood flow to the xenograft and adjacent kidney parenchyma was measured using laser Doppler flowmetry. Heat shock protein 70 (HSP70) levels in the graft were quantified by immunoassay within 2 hours of transplantation (day 0) and at days 3, 6, 9, 12 (both groups), and days 15, 40, and 85 (normoglycemic recipients only).
What was found
Graft revascularization occurred rapidly: by day 3 post-transplantation, graft blood flow reached 70% of the adjacent kidney parenchyma blood flow, eventually reaching equal or higher perfusion over time. Host hyperglycemia did not alter the rate or extent of revascularization. Baseline HSP70 levels were high in cultured ICCs prior to transplantation, but graft HSP70 content decreased markedly by days 3 to 9 in both normo- and hyperglycemic recipients and remained low thereafter.
Why it matters
The study indicates that fetal porcine islet grafts rapidly establish a functional microvasculature and experience diminished cellular stress shortly after transplantation, regardless of host blood glucose levels.
Limits
Conducted entirely in an immunodeficient (nude) rodent model, which does not account for normal xenogeneic immune rejection. The total number of mice evaluated is not reported in the abstract, and follow-up beyond 12 days was only conducted in normoglycemic animals. Endocrine efficacy and glycemic control were not reported.
Cited by
- supports Pancreatic tissue transplanted under the kidney capsule receives sufficient blood flow to survive and function.