Current treatments for T1D place a heavy burden on patients. Every day, they must measure their blood sugar levels with multiple finger pricks or wearable continuous glucose monitors (CGMs) while also calculating levels based on food intake, exercise, stress, illness, and other, often unpredictable, factors. An estimated 1.6 million people in the United States live with the disease, and studies have shown that less than one-third consistently achieve their target blood glucose levels. Patients with T1D are at higher risk for cardiovascular disease, nerve and kidney damage, and mental health issues, in addition to being more likely to experience severe hypoglycemic events that often require hospitalization and may entail seizures, unconsciousness, and even death.
Hope is on the horizon, however, with emerging regenerative medicine techniques holding significant promise of better patient outcomes while reducing or eliminating the burden of CGM and daily insulin.
Insulin Injections Are Imperfect Treatment for T1D
Although the insulin hormone was discovered a century ago, insulin injections remain an imperfect treatment for T1D, and new, improved therapies are needed. While insulin pumps and CGM have improved delivery methods, they do not eliminate the daily disease management, risks for hospitalization, and long-term complications faced by patients with T1D. Pancreas transplants, an alternative to insulin treatment, are an impractical option for most patients, given the limited supply of organs, the need for major surgery, and subsequent requirement for lifelong immunosuppressive drugs.
Around 70,000 patients in the US living with poorly controlled insulin-dependent diabetes are candidates for islet cell transplant, according to the Diabetes Research Institute. Islet cells in the pancreas contain both the beta and alpha cells responsible for glucose regulation. Regenerative medicine holds promise not only for this group, but for all patients with T1D. The approach is predicated on replacing missing insulin-producing beta cells using laboratory-developed stem cells that can be differentiated into fully functioning mature cells.
Previous research has demonstrated that transplanted islet cells from cadavers may help treat patients with T1D. These transplants showed evidence of glucose control, independence from exogenous insulin and normalization of A1C. Key findings showed that about 90% of recipients of cadaver transplants experienced no hypoglycemic events for more than 5 years, while more than 50% of recipients produced sufficient exogenous insulin during that period. Unfortunately, hurdles remain: Only about 50% of these recipients achieved insulin independence after 1 year because of autoimmune islet cell destruction. Moreover, there is a limited supply of islet cells.
New Methods for Replacing Beta Cells
Recognizing these challenges, researchers are working to solve this problem in the lab. Stem cells have the potential to differentiate into other cell types without the supply constraints of donor-derived cells, and methods for replacing beta cells are being explored, such as:
- Producing and infusing early stage, pancreatic endoderm cells that can mature into islet cells, creating both beta and alpha cells that work synchronously to control patients’ glucose levels. San Diego-based ViaCyte is developing an implantable device containing these cells, and preliminary study results demonstrated effective engraftment and production of C-peptide, a biomarker that assesses production of insulin by functional pancreatic beta cells.
- Implanting more mature, stem cell-derived islet cells into patients with T1D to restore pancreatic islet cell function.
As the field progresses, researchers continue to seek answers on where to optimally place cells in the body, as well as how to ensure their long-term safety and viability. Further preclinical and clinical evaluation is critical to identify which types of cells and delivery methods will be most effective, as well as how best to optimize strategies for using stem cell-based therapies in treating T1D.
Evading the body’s immune response to foreign cells remains a huge obstacle to these technologies. Although immunosuppressive drugs are an option, they carry serious side effects, including higher risk of infections and various cancers. Consequently, scientists are testing alternative strategies that may eliminate immune system rejection without the need for immunosuppression. Those efforts include methods to induce immune tolerance and/or to gene-edit cells to help them evade the immune system. Research on gene-editing techniques is showing promise in the development of stem cells engineered to evade immune system attacks.
Despite some obstacles, regenerative medicine approaches are poised to provide patients with T1D with potentially transformative treatments that hold the promise of a healthier, much less burdensome future. Faced with the arduous, daily task of managing their disease, many are eager to participate in clinical trials to help advance the field. To help patients make informed decisions about how they can contribute to this research, clinicians should familiarize themselves with these innovative therapies.