The Optimal Timing for Pancreatic Islet Transplantation into Subcutaneous Scaffolds Assessed by Multimodal Imaging.

Andrea Gálisová,Markéta Jirátová,Zuzana Berková,Lucie Kosinová,Vít Herynek,Eva Fábryová,Eva Sticová,Milan Hájek,Jan Kříž,Daniel Jirák

doi:10.1155/2017/5418495

Abstract

Subcutaneously implanted polymeric scaffolds represent an alternative transplantation site for pancreatic islets (PIs) with the option of vascularisation enhancement by mesenchymal stem cells (MSC). Nevertheless, a proper timing of the transplantation steps is crucial. In this study, scaffolds supplemented with plastic rods were implanted into diabetic rats and two timing schemes for subsequent transplantation of bioluminescent PIs (4 or 7 days after rod removal) were examined by multimodal imaging. The cavities were left to heal spontaneously or with 10 million injected MSCs. Morphological and vascularisation changes were examined by MRI, while the localisation and viability of transplanted islets were monitored by bioluminescence imaging. The results show that PIs transplanted 4 days after rod removal showed the higher optical signal and vascularisation compared to transplantation after 7 days. MSCs slightly improved vascularisation of the graft but hindered therapeutic efficiency of PIs. Long-term glycaemia normalisation (4 months) was attained in 80% of animals. In summary, multimodal imaging confirmed the long-term survival and function of transplanted PIs in the devices. The best outcome was reached with PIs transplanted on day 4 after rod removal and therefore the suggested protocol holds a potential for further applications.

Highlights

Intrahepatic transplantation of pancreatic islets (PIs) represents an alternative treatment for unstable type 1 diabetic patients [1], but the procedure is associated with partial damage of liver tissue [2, 3] and graft impairment due to bloodmediated inflammation, rejection, or hypoxia [4]
The bioluminescent rats were used as donors of LUC+ pancreatic islets and their LUC− littermates served as either recipients of the transplanted syngenic islets or as donors of LUC− mesenchymal stem cells (MSC)
We assessed the optimal timing for transplantation of pancreatic islets into subcutaneously preimplanted polymeric macroporous scaffolds using multimodal imaging

Summary

Introduction

Intrahepatic transplantation of pancreatic islets (PIs) represents an alternative treatment for unstable type 1 diabetic patients [1], but the procedure is associated with partial damage of liver tissue [2, 3] and graft impairment due to bloodmediated inflammation, rejection, or hypoxia [4]. Recognition of these limitations has increased the interest in the search for alternative transplantation sites in order to avoid liver-specific obstacles, provide adequate space for the transplanted islet mass, establish an efficient vascular network, restore physiological blood glucose levels, and minimise direct contact with blood [5, 6]. The scaffolds are supplemented with plastic rods to create a cavity for tissue and vessel ingrowth

Objectives

Methods

Results

Discussion

Conclusion