Introduction to promising treatment for type I diabetes

Cell therapy became a hot topic since chimeric antigen receptor (CAR) T-cell therapy was approved by U.S. Food and Drug Administration (FDA) for acute lymphoblastic leukemia and lymphomas. It is a milestone for cancer treatment, but cell therapy is also a promising solution for type 1 diabetes (T1D) patients. According to American Diabetes Association, nearly 1.6 million Americans had T1D in 2018. In each year, there are around 64,000 people diagnosed with T1D in the United States. Moreover, scientists and doctors predict that there will be 5 million T1D patients by 2050 in the United States. Additionally, according to American Diabetes Association, two different methods are used to identify diabetes, glaciated hemoglobin (A1c) test, and blood glucose test. The glaciated hemoglobin (A1c) test could indicate the average level of blood glucose in the past two to three months. The A1c level is divided into three intervals: A1c level below 5.7 is considered normal, between 5.7 and 6.4% is identified as pre-diabetes, and over 6.5% is diagnosed as diabetes. In blood glucose tests, there are three different methods to measure blood glucose: 1. Random blood glucose test: a blood sample is collected without fasting before the test, and the blood glucose less than 200-milligram per deciliter (mg/dL) is identified as normal. 2. Fasting blood glucose test: a blood sample is collected after overnight fasting. The blood glucose less than 100 mg/dL is normal, and between 100 and 125 mg/dL is considered pre-diabetes. When the blood glucose is higher than 126 mg/dL is diagnosed as diabetes. 3. Oral glucose tolerance test: After the fasting blood glucose test, a sugary solution would be provided for oral consumption. Several blood glucose tests would be measured for the next two hours. A blood glucose level less than 140 mg/dL is normal, and a level between 140 and 199 mg/dL is considered pre-diabetes. A level over 200 mg/dL is diagnosed as diabetes.

Four different tests are usually used to diagnose diabetes: Glycated hemoglobin (A1C) test, random blood glucose test, fasting blood glucose test, and oral glucose tolerance test.


T1D is an autoimmune disease; the patients’ immune system cannot recognize their own cells/tissue and attack them. In the human body, the pancreas plays an important role in maintaining the blood glucose level by two hormones, insulin, and glucagon. After each meal, blood glucose increases, and insulin is secreted to lower blood glucose. On the other hand, when a person feels hungry and the blood glucose is lower than the normal level, the alpha cells in the pancreas will secret glucagon to increase blood glucose level. However, in T1D, the pancreas is no longer functional to respond to dynamic blood glucose. In T1D patient’s daily life, insulin injection is required after every meal to prevent high glucose levels, which might cause cardiovascular disease. Up to date, researchers have been developed two potential treatments for type I diabetes, cell therapy, and artificial pancreas.

Islet cells in pancreas are comprised of different cell types: alpha cells, beta cells and delta cells. Additionally, alpha cells could respond to hypoglycemia (low blood sugar) by glucagon secretion, and beta cells could secrete insulin while hyperglycemia occurs. However, the alpha and beta cells are detroyed by T1D patient’s immune system and the body would lose the ability to maintain blood glucose level.

In cell therapy, it is a simple idea that we could transplant the pancreatic cells to replace the destroyed cells; however, the transplanted cells would be attacked by the patient’s own immune system again. To solve this, many researchers have been worked on cell encapsulation to protect the cells from immune cells attack. In 2015, Prof. Minglin Ma and his group at Cornell University developed a novel design to incorporate nano-fiber and hydrogel together to protect the pancreatic cells by hydrogel and enhance the mechanical property by stiff nano-fiber. In 2018, a retrievable and scalable cell encapsulation device was designed for the potential treatment of type I diabetes. The common design of these potential therapeutics is that the hydrogel material could not only protect the cells from antibody attack but also allow the mass transfer, such as nutrients, oxygen, insulin, to respond to blood glucose. Therefore, the transplanted cells could respond to the blood glucose immediately. On the other hand, the artificial pancreas is another option to treat type I diabetes with precise control release of insulin and glucagon to maintain blood glucose. Two methods we could use to manipulate the release, chemically and electronically management. In chemically management, a smart hydrogel is designed and synthesized to respond to the blood glucose in material property change to release glucagon in low plasma glucose and insulin in high plasma glucose. For instance, in 2020, Prof. Zhen Gu and his team at UCLA developed a dual responsive micro-needle system to manage blood glucose levels. Although the chemically responsive design is an intelligent approach to deliver the therapeutic peptides, the delivery of peptides relies on mass diffusion, which might not be effective immediately. In the electronically management, electronical device could measure the blood glucose in real time and inject the insulin or glucagon directly. However, the embedded needle of the electronical device need to be replaced every 2-3 days. In sum, cell therapy and artificial pancreas could be promising solutions to treat or “cure” type I diabetes in the future.

Hydrogel could protect the encapsulated cells from immune system and the porous structure allows mass diffusion of nutrients and waste.

Reference:

  1. Centers for Disease Control and Prevention (CDC), Nataional Diabetes Statistics Report, 2020
  2. American Diabetes Association, Statistics About Diabetes
  3. D. An et al. Developing robust, hydrogel-based, nanofiber-enabled encapsulation devices (NEEDs) for cell therapies, Biomaterials 2015
  4. D. An et al. Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes, Proceedings of the National Academy of Sciences 2018
  5. Z. Wang et al. Dual self-regulated delivery of insulin and glucagon by a hybrid patch, Proceedings of the National Academy of Sciences 2020

Jason(Yen-Chun) Lu, All right reserved.

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