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

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.

Construction of tissue engineering bone with the co‑culture system of ADSCs and VECs on partially deproteinized biologic bone in vitro: A preliminary study

“…Accurate timing of the transplantation steps (implantation of scaffolds and transplantation of cells) is important to reach sufficient vascularization and a proper level of tissue ingrowth prior to transplantation. When cells are transplanted too early, premature cells with poor adherence grow, whereas when cells are transplanted too late, cell apoptosis increases ( 33 ). The adhesion and function of ECs on smooth muscle cells in a co-culture, with the addition of fibronectin, could be consistently maintained for up to 10 days, although there was no change in the growth rate of ECs ( 34 ).…”

A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging

“…, using the vascular factors/stem cells). Moreover, the scaffolds are suitable for examining transplanted cells using various imaging methods [ 4 , 32 ]. In addition to the grafted islets being concentrated in one place, which is advantageous for in vivo imaging detection, the scaffolds are implanted subcutaneously, ensuring a short optical path for the fluorescence/bioluminescence signal emitted from the transplanted islets.…”

In Vivo Imaging of Pancreatic Islet Grafts in Diabetes Treatment

“…Thus, the use of BLI has been confined to the study of cells and tissues in small rodents. BLI has been used to monitor the effects of 3D stem cell spheroids ( 13 ), poly(ethylene glycol)-encapsulants ( 14 ), mesenchymal stem cell-enriched scaffolds ( 16 ) or heparin-releasing silk fibroin scaffolds ( 17 ) on islet survival in vivo in rodents. The overall tolerance of islets for labeling them with perfluoro-15-crown-5-ether (PCE) emulsions for 19 F MRI ( 10 ) or poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PCE and indocyanine green dye for 19 F MRI and near-infrared (NIR) fluorescence imaging ( 15 ) has also been evaluated with BLI.…”

“…For in vivo imaging, islets or cells are typically labeled prior to transplantation with the exception of SPECT and PET radiolabeling. For BLI, islets or beta-like cells, such as INS-1E cells, can be transfected or transduced with luciferase gene commonly derived from firefly (10)(11)(12)(13)(14)(15)(16)(17). Baculovirus has been used to mediate radiolabeling by 125 I for SPECT imaging (18).…”