Non-invasive quantification of stem cell-derived islet graft size and composition

Area of Science:

• Regenerative Medicine
• Medical Imaging
• Endocrinology

Background:

• Stem cell-derived islets (SC-islets) offer potential for type 1 diabetes treatment.
• Current limitations include the lack of non-invasive methods for long-term SC-islet graft monitoring.
• Positron emission tomography (PET) has shown promise for monitoring transplanted pancreatic islets.

Purpose of the Study:

• To evaluate PET as a non-invasive method for monitoring SC-islet grafts in vivo.
• To assess the utility of two PET tracers, [18F]exendin and [18F]FDOPA, for SC-islet graft assessment.
• To correlate PET findings with graft size, composition, and beta cell mass.

Main Methods:

• Human SC-islets were implanted into mouse calf muscle and monitored via PET for 5 months using [18F]exendin and [18F]FDOPA.
• Graft doses, differentiation protocols, and genetic modifications (hyper-/hypoactive) were varied.
• Histological analysis and C-peptide measurements were performed to assess graft size, composition, and function.

Main Results:

• PET successfully detected SC-islet grafts, with [18F]exendin showing higher detection rates than [18F]FDOPA, especially for small grafts (<1 mm³).
• Graft volume quantified by both tracers strongly correlated with actual graft volume (r²=0.91 for [18F]exendin, r²=0.86 for [18F]FDOPA).
• [18F]exendin uptake correlated with SC-beta cell proportion (r²=0.68), and C-peptide levels showed weak correlation with SC-beta cell mass.

Conclusions:

• [18F]exendin and [18F]FDOPA PET are effective for non-invasive assessment of SC-islet graft size and composition.
• These PET methods can provide valuable insights for optimizing SC-islet cell replacement therapy.
• The findings support the use of PET for monitoring SC-islet graft performance in diabetes treatment.