Effect of Mesenchymal Stem Cells on the Vascularization of the Artificial Site for Islet Transplantation in Rats E. Fabryova a , D. Jirak b , P. Girman c , K. Zacharovova a , A. Galisova b , F. Saudek a,c , and J. Kriz c, * a Center of Experimental Medicine, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic; b Department of MR Spectroscopy, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic; c Diabetes Center, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic ABSTRACT An adequate vascularization of the artificially created cavity is crucial for subsequent transplantation of isolated pancreatic islets. In a reported study, dynamic contrast- enhanced magnetic resonance imaging was used to assess the effect of mesenchymal stem cells on neoangiogenesis within connective tissue surrounding an implantable biocompatible device. The signal increase detected after injection of magnetic resonance contrast agent in each target region was considered to be an effect of contrast agent, which was related to the blood supply. To minimize the influence of variability in contrast agent application, all outcomes measured in the implanted devices were normalized to the signal intensity of kidney tissue. When supported by mesenchymal stem cells, the mean signal increase intra-abdominally was 42%, 41%, and 64% and within subcutaneously implanted devices was 23%, 54%, and 52% of that measured in kidney. I NTRAPORTAL transplantation of pancreatic islets is considerably limited by immediate destruction of 50% to 60% of transplanted cells due to the instant blood- mediated inflammatory reaction (IBMIR), hypoxia, high concentrations of nutrients, drugs, and toxins coming from intestines [1e4]. Great attention has been paid to the creation of an artificial site that could provide a better environment for engraftment [5]. Considering the high islet oxygen demand and the risk of IBMIR, the artificial site should be able to provide a rich vascularization without a direct contact with blood. A subcutaneous pouch created using polymeric mesh scaffold shaped into a rounded porous cylinder represents a promising option requiring only a minimally invasive surgery necessary for implantation. However, the device is covered soon with an almost avascular fibrotic tissue providing only a minimal supply of oxygen and nutrients [6]. The pouch created within the greater omentum might provide a better oxygen supply [7]. We have already reported on the monitoring of both types of pouches using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) [8]. The subcu- taneous devices were always poor in blood perfusion, but de- vices created within the greater omentum provided almost adequate blood supply for 1 week after implantation. How- ever, perfusion steadily declined later [8]. Therefore, the aim of our study was to assess the vascularization of the implantable devices after addition of mesenchymal stem cells (MSCs), which have been repeatedly described to produce in hypoxic environment the vascular endothelial growth factor (VEGF) and stimulate neo-angiogenesis [9,10]. Blood flow in the artificial devices designed for subsequent islet implanta- tion was assessed noninvasively with the use of DCE-MRI. METHODS The scaffolds (inspired by those designed by Sernova company, London, Ontario, Canada [5]) were created from silon monofil blue mesh (ELLA-CS, Hradec Kralove, Czech Republic) (Fig 1A), and under general anesthesia (ketamine 60 mg/kg, Narketan, Vétoqui- nol, Poland and dexmedetomidine 0.25 mg/kg, Dexdomitor, Orion Pharma, Finland; injected intramuscularly) were implanted both subcutaneously and into the greater omentum of male Brown Norway rats (230e270g; Charles River Germany) as was previously Supported by the grant of the Czech Ministry of Health No. NT14240-3, the project (Ministry of Health, Czech Republic) for development of research organization 00023001 (IKEM, Prague, Czech Republic) e “Institutional support,” and the Beta Train e 7 th EU Framework Program, No. 289932. *Address correspondence to Jan Kriz, MD, PhD, Diabetes Center, Institute for Clinical and Experimental Medicine, 140 21 Prague, Videnska 1958/9, Czech Republic. E-mail: jkri@ikem.cz ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2014.05.074 Transplantation Proceedings, 46, 1963e1966 (2014) 1963