Dian R Arifin1,2, Steffi Valdeig3, Robert A Anders4, Jeff W M Bulte1,2,5,6,7, Clifford R Weiss3. 1. Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. 2. Institute for Cell Engineering, Cellular Imaging Section and Vascular Biology Program, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 3. Interventional Radiology Center, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. 4. Gastrointestinal Liver Pathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. 5. Department of Chemical & Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. 6. Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. 7. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Abstract
BACKGROUND: The fate of magnetically labeled, barium-gelled alginate/protamine sulfate/alginate microcapsules (APSA magnetocapsules) following xenotransplantation was assessed by magnetic resonance imaging (MRI) and histopathology. METHODS: Magnetocapsules with and without human islets were transplanted into five different clinically accessible sites: portal vein, subcutaneous tissue, skeletal muscle, the liver and the kidney subcapsular space. The surface of APSA magnetocapsules was modified using clinical-grade heparin to mitigate an instant blood-mediated inflammatory reaction. RESULTS: The accuracy of site-specific delivery was confirmed using a clinical 1.5T MRI setup, where the magnetocapsules appeared as distinct hypointense entities after transplantation. As proven by the Lee-White blood coagulation test, heparin-treated APSA magnetocapsules did not induce blood clotting for more than 48 h in vitro. Heparinized magnetocapsules induced innate and adaptive immune responses in vivo regardless of the transplantation sites. CONCLUSION: We have demonstrated the feasibility of using a clinical 1.5T MRI to non-invasively detect the accuracy of APSA magnetocapsule injection into various clinically accessible transplantation sites. Among the investigated transplantation sites, the liver and kidney subcapsular space were found to be the least immuno-responsive toward xenografted magneto-encapsulated human islets.
BACKGROUND: The fate of magnetically labeled, barium-gelled alginate/protamine sulfate/alginate microcapsules (APSA magnetocapsules) following xenotransplantation was assessed by magnetic resonance imaging (MRI) and histopathology. METHODS: Magnetocapsules with and without human islets were transplanted into five different clinically accessible sites: portal vein, subcutaneous tissue, skeletal muscle, the liver and the kidney subcapsular space. The surface of APSA magnetocapsules was modified using clinical-grade heparin to mitigate an instant blood-mediated inflammatory reaction. RESULTS: The accuracy of site-specific delivery was confirmed using a clinical 1.5T MRI setup, where the magnetocapsules appeared as distinct hypointense entities after transplantation. As proven by the Lee-White blood coagulation test, heparin-treated APSA magnetocapsules did not induce blood clotting for more than 48 h in vitro. Heparinized magnetocapsules induced innate and adaptive immune responses in vivo regardless of the transplantation sites. CONCLUSION: We have demonstrated the feasibility of using a clinical 1.5T MRI to non-invasively detect the accuracy of APSA magnetocapsule injection into various clinically accessible transplantation sites. Among the investigated transplantation sites, the liver and kidney subcapsular space were found to be the least immuno-responsive toward xenografted magneto-encapsulated human islets.
Authors: Thomas W Link; David Woodrum; Wesley D Gilson; Li Pan; Di Qian; Dara L Kraitchman; Jeff W M Bulte; Aravind Arepally; Clifford R Weiss Journal: J Vasc Interv Radiol Date: 2011-08-04 Impact factor: 3.464
Authors: Parker H Mills; T Kevin Hitchens; Lesley M Foley; Thomas Link; Qing Ye; Clifford R Weiss; Joe D Thompson; Wesley D Gilson; Aravind Arepally; John A Melick; Patrick M Kochanek; Chien Ho; Jeff W M Bulte; Eric T Ahrens Journal: Magn Reson Med Date: 2011-06-07 Impact factor: 4.668
Authors: Sara Ponce; Gorka Orive; Rosa Hernández; Alicia R Gascón; Jose Luis Pedraz; Bart J de Haan; Marijke M Faas; H J Mathieu; Paul de Vos Journal: Biomaterials Date: 2006-10 Impact factor: 12.479
Authors: A M James Shapiro; Camillo Ricordi; Bernhard J Hering; Hugh Auchincloss; Robert Lindblad; R Paul Robertson; Antonio Secchi; Mathias D Brendel; Thierry Berney; Daniel C Brennan; Enrico Cagliero; Rodolfo Alejandro; Edmond A Ryan; Barbara DiMercurio; Philippe Morel; Kenneth S Polonsky; Jo-Anna Reems; Reinhard G Bretzel; Federico Bertuzzi; Tatiana Froud; Raja Kandaswamy; David E R Sutherland; George Eisenbarth; Miriam Segal; Jutta Preiksaitis; Gregory S Korbutt; Franca B Barton; Lisa Viviano; Vicki Seyfert-Margolis; Jeffrey Bluestone; Jonathan R T Lakey Journal: N Engl J Med Date: 2006-09-28 Impact factor: 91.245
Authors: Marcos Perez-Basterrechea; Ruben M Briones; Maria Alvarez-Viejo; Eva Garcia-Perez; Manuel M Esteban; Veronica Garcia; Alvaro J Obaya; Luis Barneo; Alvaro Meana; Jesus Otero Journal: Tissue Eng Part A Date: 2009-03 Impact factor: 3.845
Authors: Bernhard J Hering; Martin Wijkstrom; Melanie L Graham; Maria Hårdstedt; Tor C Aasheim; Tun Jie; Jeffrey D Ansite; Masahiko Nakano; Jane Cheng; Wei Li; Kathleen Moran; Uwe Christians; Colleen Finnegan; Charles D Mills; David E Sutherland; Pratima Bansal-Pakala; Michael P Murtaugh; Nicole Kirchhof; Henk-Jan Schuurman Journal: Nat Med Date: 2006-02-19 Impact factor: 53.440
Authors: Bernhard J Hering; David K C Cooper; Emanuele Cozzi; Henk-Jan Schuurman; Gregory S Korbutt; Joachim Denner; Philip J O'Connell; Harold Y Vanderpool; Richard N Pierson Journal: Xenotransplantation Date: 2009 Jul-Aug Impact factor: 3.907
Authors: Muhammad Jamal Afridi; Arun Ross; Xiaoming Liu; Margaret F Bennewitz; Dorela D Shuboni; Erik M Shapiro Journal: Magn Reson Med Date: 2016-12-26 Impact factor: 4.668
Authors: Lamar O Mair; Sagar Chowdhury; Genaro A Paredes-Juarez; Maria Guix; Chenghao Bi; Benjamin Johnson; Bradley W English; Sahar Jafari; James Baker-McKee; Jamelle Watson-Daniels; Olivia Hale; Pavel Stepanov; Danica Sun; Zachary Baker; Chad Ropp; Shailesh B Raval; Dian R Arifin; Jeff W M Bulte; Irving N Weinberg; Benjamin A Evans; David J Cappelleri Journal: Micromachines (Basel) Date: 2019-03-31 Impact factor: 2.891
Authors: Gabriel Alexander Salg; Nathalia A Giese; Miriam Schenk; Felix J Hüttner; Klaus Felix; Pascal Probst; Markus K Diener; Thilo Hackert; Hannes Götz Kenngott Journal: J Tissue Eng Date: 2019-10-30 Impact factor: 7.813