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Updated: May 30, 2026
Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres
Published on: November 5, 2016
Paramagnetic microparticles do not elicit islet cytotoxicity with co-culture or host immune reactivity after
Thomas M Suszynski1, Michael D Rizzari, Louis S Kidder
1Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN 55401, USA.
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.
Conclusion:
MPs do not adversely affect islet viability or function during co-culture, and MPs are not immune reactive following implantation.
Insights
Paramagnetic microparticles (MPs) do not harm pancreatic islet function or viability in xenotransplantation models. Studies confirmed MPs are safe for islet purification and do not trigger adverse immune responses post-implantation.
Area of Science:
- Biomedical Engineering
- Transplantation Immunology
- Cell Biology
Background:
- Paramagnetic microparticles (MPs) show potential for pancreatic islet purification, particularly for porcine islets intended for xenotransplantation.
- Assessing the impact of MPs on islet function and their safety post-implantation is crucial for xenotransplantation viability.
Purpose of the Study:
- To evaluate the effects of paramagnetic microparticles (MPs) on pancreatic islet viability and function.
- To determine if MPs induce adverse effects or immune reactions after implantation in xenotransplantation models.
Main Methods:
- Porcine islets were co-cultured with varying concentrations of MPs (0, 500, 1500 MPs/IE) for 1 and 7 days.
- Islet viability was assessed via oxygen consumption rate (OCR/DNA).
- Glucose-stimulated insulin secretion (GSIS) and in vivo function (hyperglycemia normalization in diabetic mice) were evaluated post-co-culture. Immune response was assessed after MP implantation in mice.
Main Results:
- No significant differences in islet viability (OCR/DNA) were observed after 1-day or 7-day co-culture with MPs.
- Paramagnetic microparticles did not affect glucose-stimulated insulin secretion (GSIS) in co-cultured islets.
- Implanted MPs did not cause tissue injury, inflammation, or immune reactivity, and co-cultured islets successfully normalized hyperglycemia in vivo.
Conclusions:
- Paramagnetic microparticles do not adversely affect pancreatic islet viability or function during co-culture.
- MPs demonstrate a lack of immune reactivity upon implantation, supporting their safety for xenotransplantation applications.
