Editors' ChoiceCell Transplantation

Pigs in a blanket

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Science Translational Medicine  10 Feb 2016:
Vol. 8, Issue 325, pp. 325ec24
DOI: 10.1126/scitranslmed.aaf2011

In type I diabetes, a patient’s immune system attacks the insulin-producing cell clusters of the pancreas, or pancreatic islets, resulting in an inability to regulate glucose levels in the blood and leading to many life-threatening complications. Although patients can manage the disease using insulin therapy, a strategy to transplant healthy islets into the pancreas would cure diabetes. Two bottlenecks thwart this quest: the shortage of islet donors and the propensity of donor cells to be rejected by the recipient’s immune system. Haque et al. aimed to address both of these challenges through the use of immune-camouflaged islets taken from pigs, which produce insulin similar to that of humans.

The team designed a multilayered strategy to directly modify the surfaces of the islet cells so that they were shielded from the recipient’s immune system. First, the cells were coated with gelatin—a derivative of the common extracellular matrix protein collagen—through the use of lipid anchors that physically integrated with the plasma membranes of the cells’ surfaces. Carefully chosen chemical side groups on this “artificial extracellular matrix” allowed the islets to bind together, improving stability. Next, a layer of the hydrophilic polymer poly(ethylene glycol) (PEG) was added to decrease protein adsorption and thus inhibit the ability of immune cells to recognize the transplanted cells as foreign. This molecular shielding strategy did not affect the viability of the islet cells or their ability to secrete insulin in response to glucose. When transplanted into a diabetic mouse model, the camouflaged pig islet cells maintained normal blood glucose levels for 8 days, compared with only 2 days for unmodified cells. Survival of the modified islets improved to 13 days when delivered in combination with immunosuppressive drug therapy.

Although survival of the transplanted islets will need to be further improved before use in humans, this study demonstrates that biomaterials can be used to both stabilize and improve the efficacy of xenogeneic transplants. If a similar strategy could be developed that did not require the use of immunosuppressive therapy, it would represent a major advance in the treatment of many diseases.

M. R. Haque et al., Combination strategy of multi-layered surface camouflage using hyperbranched polyethylene glycol and immunosuppressive drugs for the prevention of immune reactions against transplanted porcine islets. Biomaterials 84, 144–156 (2016). [Abstract]

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