Stable transplantation results of magnetically retracted islets: a novel method

Abstract

Aims/hypothesis. Large quantities of pure viable donor islets are necessary for clinical transplantation. At present, low yields and low viability of pancreatic islets after transplantation necessitate the use of multiple donors for a single recipient. In this study an improved method for obtaining large quantities of pure viable islets of Langerhans for transplantation was developed in the rat. Methods. Islets of Langerhans were isolated from Albino Oxford rats. The donor pancreata were perfused in situ with iron oxide, which resulted in entrapment of iron particles in the capillaries of the islets. Subsequently, the islets were isolated by magnetic retraction. Islets obtained with this method were compared with islets obtained by density gradient-isolated islets with respect to yields, purity, and insulin production capacity. Islets isolated with the magnetic retraction method were transplanted under the renal capsule of streptozotocin-induced diabetic recipients. Blood-glucose levels in the recipients were monitored for 2 months after transplantation.Results. This method yielded more pure and viable islets than the conventional protocol. No contamination of exocrine tissue was observed after isolation. Furthermore, the islets isolated by magnetic retraction stained strongly positive for insulin during the entire observation period in vitro, and produced high amounts of insulin upon a challenge with glucose. The islets that were obtained by this new protocol were suitable for safe and effective transplantation. Conclusions/interpretation. We have shown that both the quantity and quality of islets obtained with this method were sufficient to induce insulin independence in a diabetic recipient using islets from only one donor. [Diabetologia (2004) 47:55-61]

Continuous Quadrupole Magnetic Separation of Islets during Digestion Improves Purified Porcine Islet Viability

“…Further improvements and adjustments in equipment design and implementation for specific applications (e.g., xeno-, allo-, or auto-transplants) may be required and may expand the benefits observed in this early study. It should also be noted that the islet labeling methods used for this study were established in literature [38, 48], in conjunction with QMS equipment and process improvements. Additional investigation is required to enhance infusion and labeling for human and porcine islets.…”

“…Magnetic separation techniques have been used to purify islets by selective magnetic labeling of the endocrine [34, 36] or the exocrine tissue [37]. Islet yields and transplant outcomes in rats were improved when magnetic microparticles (MMPs) were preferentially entrapped within the tortuous islet microvasculature and purified using magnetic retraction [38]. Furthermore, developments in quadrupole magnetic separation (QMS) technology have shown promise for the large scale batch purification of porcine islets [39], with no observed detrimental effects on islet function due to magnetic forces or shear stresses [15, 40, 41].…”

Integrin Signaling via RGD Peptides and Anti-β1 Antibodies Confers Resistance to Apoptosis in Islets of Langerhans

“…They were anesthetized by a subcutaneous injection that contained a mixture of hypnorm and dormicum in PBS. The islets of Langerhans were isolated with the magnetic retraction technique (23). In brief, the descending aorta was perfused with a freshly sonicated 1.25% suspension of Fe 3 O 4 (Sigma-Aldrich, Zwijndrecht, the Netherlands) in PBS, after the thoracic aorta had been clamped.…”

Engineering quadrupole magnetic flow sorting for the isolation of pancreatic islets

“…More recently, however, a method for magnetically labeling islets has been identified that eliminates the need for antibody labeling. In this new method, which has been adapted to the separation of other types of tissue, magnetic microparticles are infused into the vascular structure of the pancreas where they embolize in the islet capillaries [20]. By proper selection and sizing of microparticles, this ''labeling'' process can be made specific to the islets in the pancreas.…”