Just as insulin therapy revolutionized life for people with type 1 diabetes (T1D) a century ago, a new implant may one day do the same by tackling the disease’s biggest challenge—keeping transplanted insulin-producing cells alive long enough to restore normal blood sugar.
In type 1 diabetes, the body’s immune system turns against itself, destroying the pancreatic β-cells that produce insulin. “Without insulin, the body has no way to deliver glucose—sugar—into muscle and tissue cells to generate energy,” Minglin Ma, PhD, a professor of biological and environmental engineering in the College of Agriculture and Life Sciences (CALS) at Cornell University and the paper’s senior author, explained. People with T1D manage the condition through daily insulin injections or pumps, but even with treatment, the disease can lead to “life-threatening complications including severe hypoglycemia events and irreversible organ damage caused by chronic hyperglycemia,” the study noted.
Cell replacement therapy has shown promise, but most patients must take lifelong immunosuppressive drugs to prevent rejection. “…developing an immunosuppression-free strategy to protect the transplanted cells is imperative to fully harness the potential of cell therapy for curing T1D,” the authors wrote.
One such strategy is macroencapsulation, in which insulin-producing cells are housed within a semipermeable device that shields them from the immune system while allowing glucose, insulin, nutrients, and metabolic wastes to diffuse. Yet these systems often fail because the encapsulated cells have insufficient oxygen. “One of the major challenges is that the implant itself often dies due to the lack of oxygen after implantation,” co-first author Lora (Phuong) Tran, a PhD candidate at Cornell, said. “In our lab, they had success in mice that lived over one year, and they controlled the diabetes very effectively with some small capsules without oxygen generation. However, when we scale up, we need more cells, we need more density, especially. We need a higher dose. If we implant without generating oxygen, the cells often die within two weeks.”
Ma’s lab, in collaboration with Giner, developed the BioElectronics-Assisted Macroencapsulation (BEAM) system, described in the paper, “A continuously oxygenated macroencapsulation system enables high-density packing and delivery of insulin-secreting cells,” recently published in Nature Communications. The platform combines “a miniaturized implantable electrochemical oxygen generator (iEOG) with a scalable, linear cell pouch designed for minimally invasive implantation and retrieval.”
The iEOG “enables continuous oxygen supply via electrolysis of tissue moisture,” delivering oxygen through a silicone tube that runs through the cylindrical cell pouch. The capsules are engineered to be “immune protective and last for a long time without… fouling of the membrane,” co-author Linda Tempelman, PhD, said.
In vitro, the BEAM system kept both rat insulinoma (INS-1) cell aggregates and primary human pancreatic islets alive and functional under severe hypoxia (one percent oxygen) at a high packing density of 60,000 islet equivalents per milliliter. Non-oxygenated controls showed “significant cell death… and almost no insulin-positive cells” within 24 hours.
In an allogeneic rat model, the oxygenated system reversed diabetes “for up to three months without immunosuppression, while non-oxygenated controls remained hyperglycemic,” wrote the authors. When oxygenation stopped, blood glucose spiked “right after oxygenation cessation…[suggesting] that a continuous supply of oxygen may be vital for the long-term function of pancreatic islets in cell encapsulation systems.”
This is the proof of concept, Tempelman said. “We really proved that oxygenation is important, and oxygenation will support high cell-density capsules.”
The team plans to scale up to pig studies and eventually human trials. Tempelman envisions broader applications: “We see an age where people will be getting implants with allogeneic cells… long term to treat things that your body is missing.”
For the two million Americans with T1D, the BEAM system could someday shift cell therapy from experimental to routine care, bringing a century-old dream of an insulin-free life closer to reality.