In patients with diabetes, the immune system attacks the pancreas, eventually leaving patients without the ability to naturally control blood sugar. These patients must carefully monitor the amount of sugar in their blood, and then inject themselves with insulin to keep their blood sugar levels within a healthy range. However, precise control of blood sugar is difficult to achieve, and patients face a range of long-term medical problems as a result. Now, a study from researchers at MIT is develops a ‘living drug factory’, an implantable, long-term insulin-producing device which may one day make injections obsolete. The team state their living drug factories, made of encapsulated, engineered cells, can be safely implanted in the body to produce insulin over the course of months or even years. The archive of studies are published in Nature Materials, Nature Biotechnology, Nature Materials, and Nature Medicine.
Past studies from the group have investigated new technological approaches toward islet cell encapsulation, to develop commercially viable cell-encapsulation technology for diabetes. The issue was identifying the right material which protected cells but made them, essentially, invisible to the immune system. Most materials placed in the body lead to scar tissue accumulation, a process called fibrosis. The current study develops a material that encapsulates human islet cells before transplanting them, and could cure diabetes for up to six months, without provoking an immune response.
The current study chemically modifies alginate, a polysaccharide which lines the cell walls of brown algae; when combined with water, alginate can also be made into a gel which can safely encapsulate cells without limiting function. Results show that molecules containing a triazole group which the lab attached to the alginate’s polymer chain ensure that the coating didn’t cause fibrosis or provoke an immune response.
The group state that the pancreatic islet cells used in the study were generated from human stem cells. Data findings show that following implantation, the cells immediately began producing insulin in response to blood sugar levels and were able to keep blood sugar under control for the length of the study, 174 days. Results show that the cells can sense glucose and secrete insulin in a controlled manner, alleviating the mice’s need for injected insulin. The lab also observed that 1.5-millimeter diameter capsules made from their best materials could be implanted into the intraperitoneal space of nonhuman primates for at least six months without scar tissue building up.
The team surmise they have developed a living drug factory based on a hydrogel that keeps cells alive and is permeable so that sugar and nutrients can come in and insulin can go out, without causing an acute immune response. For the future, the researchers state they are working on various other applications, including ‘sense and respond’ therapies, where cells sense biological signals and respond with precise dosage of a target therapeutic.