Short Communication Paramagnetic microparticles do not elicit islet cytotoxicity with co-culture or host immune reactivity after implantation Introduction Pancreatic islet transplantation has considerable promise in reversing the diabetic state in patients with type 1 diabetes. However, consistent outcomes over the long term have been largely elusive [1–3]. Among possible reasons for this is the need for transplantation of higher numbers of islets and better quality islets. It is widely accepted that a sufficient viable b-cell mass needs to be Suszynski TM, Rizzari MD, Kidder LS, Mueller K, Chapman CS, Kitzmann JP, Pongratz RL, Cline GW, Todd PW, Kennedy DJ, O’Brien TD, Avgoustiniatos ES, Schuurman H-J, Papas KK. Paramagnetic microparticles do not elicit islet cytotoxicity with co-culture or host immune reactivity after implantation. Xenotransplantation 2011; 18: 239–244. Ó 2011 John Wiley & Sons A/S. Abstract: Background: Paramagnetic microparticles (MPs) may be useful in pancreatic islet purification, in particular purification of por- cine islets as a potential xenotransplantation product. We assessed whether MPs affect islet function or induce an adverse effect following implantation. Methods: Porcine islets were co-cultured with 0, 500, and 1500 MPs per islet equivalent (IE) for 1 day and with 0 and 1500 MPs/IE for 7 days. Fractional viability was assessed using oxygen consumption rate nor- malized to DNA content (OCR/DNA) and after 7-day co-culture by perifusion glucose-stimulated insulin secretion (GSIS) and by trans- plantation under the renal capsule of diabetic nude mice. To assess an inflammatory response or immune reaction, MPs (10 7 ) were implanted under the renal capsule of C57BL/6 mice. Results: No statistically significant differences were measured in OCR/ DNA (mean ± SE) following 1-day co-culture with 0, 500, or 1500 MPs/IE (243.3 ± 4.5, 211.3 ± 8.1, or 230.6 ± 11.3 nmol/min- ÆmgDNA, respectively) or following 7-day co-culture with 0 or 1500 MPs/IE (248.5 ± 1.4 or 252.9 ± 4.7 nmol/minÆmgDNA, respectively). GSIS was not affected by the presence of MPs; first- and second-phase insulin area-under-the-curve (mean ± SE) reflected no statistically sig- nificant differences after 7-day co-culture between 0 and 1500 MPs/IE (8.36 ± 0.29 and 8.45 ± 0.70 pg/mlÆminÆngDNA for first-phase; 69.73 ± 2.18 and 65.70 ± 4.34 pg/mlÆminÆngDNA for second-phase, respectively). Islets co-cultured with MPs normalized hyperglycemia in diabetic nude mice, suggesting no adverse effects on in vivo islet func- tion. Implantation of MPs did not elicit tissue injury, inflammatory change or immune reactivity. Conclusion: MPs do not adversely affect islet viability or function during co-culture, and MPs are not immune reactive following implantation. Thomas M. Suszynski, 1 Michael D. Rizzari, 1,2 Louis S. Kidder, 1 Kate Mueller, 1 Christopher S. Chapman, 1 Jennifer P. Kitzmann, 1 Rebecca L. Pongratz, 3 Gary W. Cline, 3 Paul W. Todd, 4,5 David J. Kennedy, 5 Timothy D. O'Brien, 6 Efstathios S. Avgoustiniatos, 1 Henk-Jan Schuurman 1 and Klearchos K. Papas 1 1 Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, 2 Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, 3 Division of Endocrinology, Department of Medicine, Yale University, New Haven, CT, 4 Techshot, Inc., Greenville, IN, 5 IKOTech, LLC, New Albany, IN, 6 Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA Key words: islet purification – islet xenotransplantation – magnetic separation – paramagnetic microparticles – quadrupole magnetic sorting Abbreviations: AUC, area-under-the-curve; IE, islet equivalent; GSIS, glucose-stimulated insulin secre- tion; MP, microparticle; OCR, oxygen consumption rate; OCR/DNA, oxygen consumption rate normal- ized to DNA content. Address reprint requests to Henk-Jan Schuurman, 111 Marquette Avenue South #3103, Minneapolis, MN 55401, USA (E-mail: schuurman2@planet.nl) Received 4 May 2011; Accepted 22 June 2011 Xenotransplantation 2011: 18: 239–244 Printed in Singapore. All rights reserved doi: 10.1111/j.1399-3089.2011.00648.x Ó 2011 John Wiley & Sons A/S XENOTRANSPLANTATION 239