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A selective decrease in the beta cell mass of human islets transplanted into diabetic nude mice

A M Davalli1, Y Ogawa, C Ricordi

  • 1Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.

Transplantation
|March 27, 1995
PubMed
Summary
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Human islet transplantation in diabetic mice rapidly improved blood glucose and weight. However, beta cell mass significantly decreased post-transplant, while nonbeta cells remained stable, altering the graft composition.

Area of Science:

  • Endocrinology
  • Transplantation Biology
  • Metabolic Research

Background:

  • Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells.
  • Islet transplantation is a potential therapeutic strategy for type 1 diabetes.
  • Understanding graft survival and composition is crucial for successful islet transplantation.

Purpose of the Study:

  • To investigate the changes in beta cell and nonbeta cell mass in human islet grafts transplanted into diabetic nude mice.
  • To assess the impact of these changes on graft function and composition over time.

Main Methods:

  • Human islet equivalents (IE) were transplanted under the kidney capsule of streptozocin-induced diabetic nude mice.
  • Blood glucose levels and body weight were monitored for up to 30 days.

Related Experiment Videos

  • Islet graft composition (beta cell and nonbeta cell mass) was quantified using morphometry and immunohistochemistry.
  • Beta cell replication was assessed by bromo-2' deoxyuridine (BrdU) incorporation.

    • Main Results:

    • Islet transplantation led to rapid normalization of blood glucose and increased body weight.
    • A significant decrease in beta cell mass was observed within 15 and 30 days post-transplantation.
    • Endocrine nonbeta cell mass remained stable throughout the study period.
    • The nonbeta cell/beta cell ratio increased significantly over time, indicating a shift in graft composition.
    • Beta cell replication rates were low and did not significantly change between 15 and 30 days.

    Conclusions:

    • Human islet grafts experience a substantial loss of beta cell mass shortly after transplantation, even after revascularization.
    • Engrafted nonbeta cells demonstrate greater stability compared to beta cells.
    • The increasing nonbeta/beta cell ratio over time suggests potential alterations in graft structure that may influence function.