Calcium phosphate cement chamber as an immunoisolative device for bioartificial pancreas: in vitro and preliminary in vivo study

Pancreas. 2010 May;39(4):444-51. doi: 10.1097/MPA.0b013e3181be2f95.

Abstract

Objectives: This study examined a calcium phosphate cement (CPC) chamber as an immunoisolative device to facilitate the use of xenogeneic cell sources without immunosuppression for the bioartificial pancreas (BAP).

Methods: Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a CPC chamber to create a BAP. Bioartificial pancreas were evaluated by cell viability, live-dead cell ratio, and cytokine-mediated cytotoxicity assay and implanted into the peritoneal cavity of diabetic rats. Nonfasting blood glucose and serum insulin levels were analyzed perioperatively; BAPs were also retrieved for histological examination.

Results: Insulinoma cells enclosed in the CPC chamber had normal viability, cell survival, and insulin secretion that was even cultured in media with cytokines. The nonfasting blood glucose level of rats was decreased from 460 +/- 50 to 132 +/- 43 mg/dL and maintained euglycemia for 22 days; serum insulin level was increased from 0.34 +/- 0.11 to 1.43 +/- 0.30 microg/dL after operation. Histological examination revealed the fibrous tissue envelopment, and immune-related cells that competed for oxygen resulting in hypoxia could be attributed to the dysfunction of BAPs.

Conclusions: This study proved the feasibility for using a CPC chamber as an immunoisolative device for the BAP. An alternative implanted site should be considered to extend the functional longevity of BAPs in further study.

MeSH terms

  • Animals
  • Artificial Organs*
  • Blood Glucose / metabolism
  • Calcium Phosphates / chemistry*
  • Cell Culture Techniques / instrumentation
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / metabolism*
  • Insulin / metabolism
  • Insulin Secretion
  • Insulinoma / metabolism
  • Insulinoma / pathology
  • Interleukin-1beta / pharmacology
  • Mice
  • Pancreas / immunology
  • Pancreas / metabolism*
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Blood Glucose
  • Calcium Phosphates
  • Insulin
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • calcium phosphate