February 2, 2016

Encapsulated cells treat diabetes in mice

At a Glance

  • Researchers developed a material to encase human insulin-producing cells and protect them from the immune system.
  • When transplanted into diabetic mice, the encapsulated cells treated the diabetes without triggering an immune reaction.
  • The findings are a step forward in achieving long-term therapy for people with type 1 diabetes.
Cells in alginate capsule Insulin-producing cells, derived from stem cells, protected inside an alginate capsule engineered to be invisible to the host immune system. Cell nuclei are stained blue.Omid Veiseh and Andrew Bader, Anderson/Langer Laboratory, Koch Institute at MIT

Diabetes is a disorder in blood glucose levels. Glucose is a sugar that serves as fuel for the body. When blood glucose levels rise, beta cells in the pancreas normally make and secrete the hormone insulin. Insulin triggers cells throughout the body to take up sugar from the blood. In type 2 diabetes, the most common form, tissues in the body lose their sensitivity to insulin, and pancreatic beta cells can’t make enough insulin to keep glucose levels in check. In type 1 diabetes, the body’s own immune system attacks and destroys beta cells. High blood glucose levels can lead to heart and kidney diseases, blindness, and other health problems over time. 

Strategies to treat type 1 diabetes include replacing destroyed beta cells with human pancreatic cells transplanted from deceased donors. However, such therapies have limitations, including a lack of tissue availability and the need for the recipient to undergo therapy to prevent the donor tissue from being attacked by the immune system.

To treat diabetes without triggering an immune reaction, a multidisciplinary team set out to develop a material that encases functional cells and protects them from the immune system. The group, led by Dr. Daniel G. Anderson from Massachusetts Institute of Technology, involved scientists from several institutions. The work was funded in part by several NIH components. Results appeared online on January 25, 2016, in Nature Medicine and Nature Biotechnology.

The group used functioning beta cells developed from a human embryonic stem cell line. The cells, which are plentiful, work like normal pancreatic beta cells. They’re responsive to glucose and produce insulin, giving them the potential to restore normal blood glucose levels.

The team designed spheres to encase the cells using alginate. This hydrogel material is low cost, has low toxicity, and is used in many biomedical applications such as drug delivery and tissue regeneration. The scientists developed chemically modified alginate spheres and tested them in rodents and non-human primates. The spheres were porous enough to allow encased cells to detect surrounding glucose levels and had a surface that prevented recognition by immune cells. 

The team transplanted cells encapsulated inside the alginate spheres into mice with type 1 diabetes. Blood glucose levels and insulin production normalized to levels found in healthy mice. Control of glucose levels was maintained for almost 6 months, at which point the implants were removed for analysis. The retrieved cell clusters still produced insulin, and the alginate spheres showed minimal signs of immune attack.

The scientists plan to continue testing and refining their system in various animal models. “Our goal is to continue to work hard to translate these promising results into a therapy that can help people,” Anderson says. 

—by Carol Torgan, Ph.D.

Related Links

Reference: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta-Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister-Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R, Anderson DG. Nat Med. 2016 Jan 25. doi: 10.1038/nm.4030. [Epub ahead of print]. PMID: 26808346.
Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Vegas AJ, Veiseh O, Doloff JC, Ma M, Tam HH, Bratlie K, Li J, Bader AR, Langan E, Olejnik K, Fenton P, Kang JW, Hollister-Locke J, Bochenek MA, Chiu A, Siebert S, Tang K, Jhunjhunwala S, Aresta-Dasilva S, Dholakia N, Thakrar R, Vietti T, Chen M, Cohen J, Siniakowicz K, Qi M, McGarrigle J, Lyle S, Harlan DM, Greiner DL, Oberholzer J, Weir GC, Langer R, Anderson DG. Nat Biotechnol. 2016 Jan 25. doi: 10.1038/nbt.3462. [Epub ahead of print]. PMID: 26807527.

Funding: NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Cancer Institute (NCI), National Institute of Dental & Craniofacial Research (NIDCR), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); JDRF; Leona M. and Harry B. Helmsley Charitable Trust; Tayebati Family Foundation; Department of Defense; Harvard Stem Cell Institute; Chicago Diabetes Project; MIT SkolTech Initiative; Joslin Diabetes Research Center; and the Diabetes Research and Wellness Foundation.