Combinations of growth factors enhance the potency of islets in vitro

Pancreas. 2009 May;38(4):447-53. doi: 10.1097/MPA.0b013e318197a62e.

Abstract

Objectives: Recent studies have demonstrated the impressive expansion of beta cells in vitro. But unfortunately, expanded beta cells do not function in the same way as fully differentiated beta cells. Therefore, we developed a condition that would allow islet cells to proliferate while maintaining their endocrine function.

Methods: We tested the different use of growth factors in a different culture period. And we tested the possibility of adult islets, which expanded during a short period, as a clinical source of islet cells by comparing the efficiency of transplantation of cultured islets with that of fresh islets.

Results: The islets showed a time-dependent increase in proliferative activity, reaching 32.2% on day 5. After 5 days of culture, the efficiency of transplantation of cultured islets was increased (2-fold) in comparison to that of noncultured islets. Moreover, islet transplantation immediately induced normoglycemia at a level equal to native islets.

Conclusions: These findings suggest that adult beta cells have the potential to proliferate while maintaining their endocrine function, which can be improved through careful regulation of proliferation and differentiation.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cell Culture Techniques
  • Cell Proliferation / drug effects*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / surgery
  • Epidermal Growth Factor / pharmacology*
  • Female
  • Glucagon / metabolism
  • Hepatocyte Growth Factor / pharmacology*
  • Immunohistochemistry
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans Transplantation / methods
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Confocal
  • Rats
  • Rats, Sprague-Dawley
  • Somatostatin / metabolism
  • Time Factors
  • Transplantation, Heterologous

Substances

  • Blood Glucose
  • Insulin
  • Somatostatin
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor
  • Glucagon