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.

• MeSH
• alografty MeSH
• experimentální diabetes mellitus * diagnostické zobrazování   chirurgie   MeSH
• krysa rodu Rattus MeSH
• Langerhansovy ostrůvky * krevní zásobení   diagnostické zobrazování   metabolismus   patologie   MeSH
• luminiscenční měření * MeSH
• mezenchymální kmenové buňky metabolismus   patologie   MeSH
• potkani transgenní MeSH
• přežívání štěpu * MeSH
• tkáňové podpůrné struktury * MeSH
• transplantace Langerhansových ostrůvků metody   MeSH
• transplantace mezenchymálních kmenových buněk MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: An artificial site for cell or pancreatic islet transplantation can be created using a polymeric scaffold, even though it suffers subcutaneously from improper vascularisation. A sufficient blood supply is crucial for graft survival and function and can be enhanced by transplantation of mesenchymal stem cells (MSCs). The purpose of this study was to assess the effect of syngeneic MSCs on neoangiogenesis and cell engraftment in an artificial site by multimodal imaging. PROCEDURES: MSCs expressing a gene for luciferase were injected into the artificial subcutaneous site 7 days after scaffold implantation. MRI experiments (anatomical and dynamic contrast-enhanced images) were performed on a 4.7-T scanner using gradient echo sequences. Bioluminescent images were acquired on an IVIS Lumina optical imager. Longitudinal examination was performed for 2 months, and one animal was monitored for 16 months. RESULTS: We confirmed the long-term presence (lasting more than 16 months) of viable donor cells inside the scaffolds using bioluminescence imaging with an optical signal peak appearing on day 3 after MSC implantation. When compared to controls, the tissue perfusion and vessel permeability in the scaffolds were significantly improved at the site with MSCs with a maximal peak on day 9 after MSC transplantation. CONCLUSIONS: Our data suggest that the maximal signal obtained by bioluminescence and magnetic resonance imaging from an artificially created site between 3 and 9 days after MSC transplantation can predict the optimal time range for subsequent cellular or tissue transplantation, including pancreatic islets.

• Klíčová slova
• Bioluminescence, DCE, Dynamic contrast-enhanced MRI, Magnetic resonance imaging, Mesenchymal stem cells, Vascularisation,
• MeSH
• kontrastní látky MeSH
• luminiscenční měření MeSH
• magnetická rezonanční tomografie MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• multimodální zobrazování * MeSH
• potkani inbrední LEW MeSH
• regionální krevní průtok fyziologie   MeSH
• reprodukovatelnost výsledků MeSH
• tkáňové podpůrné struktury MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• umělé buňky * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kontrastní látky MeSH