Multimodal Imaging Reveals Improvement of Blood Supply to an Artificial Cell Transplant Site Induced by Bioluminescent Mesenchymal Stem Cells

Abstract

PurposeAn 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.ProceduresMSCs 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.ResultsWe 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.ConclusionsOur 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.

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

“…Because subcutaneous vascularisation is insufficient for islets, several approaches have been advanced with the aim of improving neoangiogenesis, such as the incorporation of vascular endothelial and fibroblast growth factors [ 17 ] and mesenchymal stem cells (MSCs) [ 10 , 18 ]. Our previous studies have also confirmed the improvement of blood supply in scaffolds induced by MSCs [ 15 , 19 ]. In other models, cotransplantation of pancreatic islets in conjunction with MSCs have resulted in improved graft revascularisation, graft survival, and better transplantation outcomes [ 20 , 21 ].…”

“…Microvascular density (MVD) assessment was performed on four serial sections from each scaffold. MVD was evaluated as the number of CD31-positive microvessels counted at a magnification of ×400 as previously described [ 19 ]. The results were expressed as the mean microvessel count with standard deviation.…”

“…Nevertheless, accurate timing of the transplantation steps (implantation of scaffolds, transplantation of MSCs/islets) is crucial in order to reach sufficient vascularisation and a proper level of tissue ingrowth prior to PIs transplantation [ 11 , 23 ]. Our previous experiments showed that the best engraftment period for PIs in the case of macroporous scaffolds is between day 3 and day 9 after rod removal [ 19 ].…”

Comunicação exossomal na transdiferenciação de células-tronco em cocultivo com células neuronais

“…Porém, esse resultado não foi devido à quantidade utilizada, pois a quantidade de células-tronco diferenciadas ou não (5x10 5 células por animal), aplicadas na lesão se assemelhou a outro estudo (GÁLISOVÁ et al, 2017), e foi efetiva uma vez que se observou diferenças, como melhora funcional e no local da lesão naqueles animais que as receberam.…”

“…Observou-se que ao terceiro dia foi quando mais se adquiriu melhores avaliações da bioluminescência, que foi decaindo com o passar do tempo (GÁLISOVÁ et al, 2017). No presente estudo o tratamento com ADSC-CC D7 resultou em redução do processo degenerativo dos axônios, o que indicou mais uma funcionalidade in vivo das ASDC além da relatada anteriormente.…”