Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets

Abstract

Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host's immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device. APA microcapsules demonstrated higher mechanical integrity and stability than A microcapsules, showing better pseudoislets viability and biological function. Importantly, we obtained a reduction of the graft volume of 77.5% for A microcapsules and 78.6% for APA microcapsules. After subcutaneous implantation of induced diabetic Wistar rats with magnetically purified APA microencapsulated pseudoislets, blood glucose levels were restored into normoglycemia (<200mg/dL) for almost 17 weeks. In conclusion, our described microfluidic magnetic sorting device represents a great alternative approach for the graft volume reduction of microencapsulated pseudoislets and its application in T1DM disease.

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…Espona-Noguera et al followed a different approach in which IONP-loaded INS1E pseudoislets were encapsulated in alginate and alginate-poly-L-lysine-alginate (APA) microcapsules [ 582 ]. Prior to transplantation, removal of empty microcapsules by a microfluidic magnetic sorting device was performed to reduce transplant volume.…”

Tissue Engineering Strategies for Improving Beta Cell Transplantation Outcome

“…In strategies such as microencapsulation, the volume of the transplanted islets is lower than the volume of the hydrogel material due to the possible presence of empty micro-capsules within the cell/capsule mix [131]. In this case, some hydrogels such as alginate, which is widely used for encapsulation procedures, can generate foreign body responses, amyloid formation, and fibrosis, leading to device failure [132,133]. Nanoencapsulation technology can be more beneficial as each capsule is fabricated according to the size and shape of an islet.…”

Review of Advanced Hydrogel-Based Cell Encapsulation Systems for Insulin Delivery in Type 1 Diabetes Mellitus

“…The use of alginate-based microcapsules containing pancreatic islets in the T1DM treatment has shown great promise since many studies have shown the successful restoration of the blood glucose levels in diabetic animal models [64].…”

“…In this regard, aiming to reduce the microcapsules graft volume, separation of microencapsulated islets from non-therapeutic microcapsules is usually accomplished by hand selection; however, the separation procedure is slow and tedious, thus complicating its reproducibility [77,78]. Recently, a novel microcapsule sorting system allows for the separation of magnetically labeled microencapsulated islets from empty microcapsules [64]. This purification system is based on a magnetic separation through a microfluidic device containing magnets, which guide the magnetized microencapsulated islets towards an output channel, while the empty microcapsules are eliminated through a different output channel.…”