Encapsulation of human islets in novel inhomogeneous alginate-ca2+/ba2+ microbeads: in vitro and in vivo function

Artif Cells Blood Substit Immobil Biotechnol. 2008;36(5):403-20. doi: 10.1080/10731190802369755.

Abstract

Microencapsulation may allow for immunosuppression-free islet transplantation. Herein we investigated whether human islets can be shipped safely to a remote encapsulation core facility and maintain in vitro and in vivo functionality. In non-encapsulated islets before and encapsulated islets after shipment, viability was 88.3+/-2.5 and 87.5+/-2.7% (n=6, p=0.30). Stimulation index after static glucose incubation was 5.4+/-0.5 and 6.3+/-0.4 (n=6, p=0.18), respectively. After intraperitoneal transplantation, long-term normoglycemia was consistently achieved with 3,000, 5,000, and 10,000 IEQ encapsulated human islets. When transplanting 1,000 IEQ, mice returned to hyperglycemia after 30-55 (n=4/7) and 160 days (n=3/7). Transplanted mice showed human oral glucose tolerance with lower glucose levels than non-diabetic control mice. Capsules retrieved after transplantation were intact, with only minimal overgrowth. This study shows that human islets maintained the viability and in vitro function after encapsulation and the inhomogeneous alginate-Ca(2+)/Ba(2+) microbeads allow for long-term in vivo human islet graft function, despite long-distance shipment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Alginates / metabolism*
  • Animals
  • Barium / metabolism
  • Blood Glucose / analysis
  • Calcium / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / surgery*
  • Drug Compounding* / instrumentation
  • Drug Compounding* / methods
  • Female
  • Glucose Tolerance Test
  • Glucuronic Acid / chemistry
  • Glucuronic Acid / metabolism
  • Hexuronic Acids / chemistry
  • Hexuronic Acids / metabolism
  • Humans
  • Immunosuppression Therapy
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Islets of Langerhans Transplantation*
  • Male
  • Mice
  • Mice, Nude
  • Microspheres*
  • Organ Preservation

Substances

  • Alginates
  • Blood Glucose
  • Hexuronic Acids
  • Insulin
  • Barium
  • Glucuronic Acid
  • Calcium