title: Paramagnetic microparticles do not elicit islet cytotoxicity with co-culture or host immune reactivity after implantation.
abstract: BACKGROUND
  Paramagnetic microparticles (MPs) may be useful in pancreatic islet purification, in particular purification of porcine 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 normalized to DNA content (OCR/DNA) and after 7-day co-culture by perifusion glucose-stimulated insulin secretion (GSIS) and by transplantation 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·mgDNA, respectively) or following 7-day co-culture with 0 or 1500 MPs/IE (248.5 ± 1.4 or 252.9 ± 4.7 nmol/min·mgDNA, respectively). GSIS was not affected by the presence of MPs; first- and second-phase insulin area-under-the-curve (mean ± SE) reflected no statistically significant differences after 7-day co-culture between 0 and 1500 MPs/IE (8.36 ± 0.29 and 8.45 ± 0.70 pg/ml·min·ngDNA for first-phase; 69.73 ± 2.18 and 65.70 ± 4.34 pg/ml·min·ngDNA for second-phase, respectively). Islets co-cultured with MPs normalized hyperglycemia in diabetic nude mice, suggesting no adverse effects on in vivo islet function. Implantation of MPs did not elicit tissue injury, inflammatory change or immune reactivity.
  
  
  CONCLUSIONS
  MPs do not adversely affect islet viability or function during co-culture, and MPs are not immune reactive following implantation.
authors.affiliation: Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN 55401, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Suszynski
authors.forename: Michael D
authors.initials: MD
authors.lastname: Rizzari
authors.forename: Louis S
authors.initials: LS
authors.lastname: Kidder
authors.forename: Kate
authors.initials: K
authors.lastname: Mueller
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chapman
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Kitzmann
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Pongratz
authors.forename: Gary W
authors.initials: GW
authors.lastname: Cline
authors.forename: Paul W
authors.initials: PW
authors.lastname: Todd
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Brien
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Avgoustiniatos
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: Klearchos K
authors.initials: KK
authors.lastname: Papas
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D005260:Female; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology* / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D060328:Magnetic Phenomena; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008863:Microspheres; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D007328:Insulin