Intramedullary cavity as an implant site for bioartificial pancreas: an in vivo study on diabetic canine

Transplantation. 2010 Sep 27;90(6):604-11. doi: 10.1097/TP.0b013e3181ca64d1.

Abstract

Background: Fibrous tissue outgrowth and hypoxia are the major restrictions for the application of bioartificial pancreas (BAP). Accordingly, the intramedullary cavity is proposed as an implant site, and a BAP constructed of calcium phosphate cement chamber was implanted.

Methods: Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a calcium phosphate cement chamber to fabricate a BAP. BAPs were implanted in the femoral intramedullary cavity of diabetic dogs. Pre- and postprandial blood glucose levels were monitored perioperatively. Blood samples were collected for the analysis of C-peptide level, and physiological conditions were observed at predetermined intervals. BAPs were retrieved at 12 weeks postoperatively for histologic examination.

Results: Preprandial blood glucose level of diabetic dogs decreased from 420 ± 25 to 223 ± 47 mg/dL at 1 day postoperatively and was maintained in the range of 259 ± 36 mg/dL for 12 weeks. As serum C-peptide level increased from 5.3 ± 2.8 to 105.7 ± 19.4 pmol/L, the rate of decrease of postprandial blood glucose was accelerated. Histologic examination revealed that recipient bone tissues were binding to the surfaces of BAPs directly; there was no development of fibrous tissue. Immunohistochemical stain was positive for insulin in the enclosed insulinoma cells.

Conclusions: This study demonstrated that BAPs implanted into the intramedullary cavity functioned well during the experimental period. Thus, the intramedullary cavity can serve as an implant site for BAPs.

MeSH terms

  • Animals
  • Artificial Organs / statistics & numerical data*
  • Blood Glucose / metabolism*
  • C-Peptide / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / surgery*
  • Dogs
  • Female
  • Humans
  • Insulinoma
  • Islets of Langerhans / pathology
  • Male
  • Mice
  • Pancreas Transplantation / methods*
  • Pancreas Transplantation / pathology
  • Tissue Donors / supply & distribution

Substances

  • Blood Glucose
  • C-Peptide