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

摘要

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.