World’s first: stem cell therapy reverses diabetes

Diabetes is a group of disorders characterized by the body’s inability to adequately make or use insulin; the hormone required to convert food into energy. There is currently no known cause of diabetes, and no treatment exists. Currently, diabetes is the seventh leading cause of death in the US.

According to the American Diabetes Association, 23.6 million adults and children in the country—or 7.8% of the total population—have diabetes. 17.9 million people are thought to have been diagnosed with diabetes; nevertheless, 5.7 million people, or over 25% of the population, do not know they have the disease. The global burden of diabetes is rising, especially in developing nations like India, China, and parts of Africa. This leads to increased healthcare costs and suffering. New treatments are emerging rapidly, including drugs like GLP-1 mimetics, DPP-4 inhibitors, and SGLT2 inhibitors. Surgical options like gastric surgeries and pancreas or islet transplants and stem cell therapy from own reprogrammed stem cells.

There are three primary classifications of diabetes:

• Type 1 is an autoimmune disorder.

• Type 2 is linked to genetic and lifestyle risk factors.

• Gestational diabetes manifests throughout pregnancy.

Type 1 Diabetes is characterized by the body’s inability to produce insulin, necessitating daily insulin injections. Because it is more common among children, it is frequently referred to as “juvenile diabetes.” According to the Juvenile Diabetes Research Foundation (JDRF), over three million Americans may have type 1 diabetes (T1D), with an average of 40 children diagnosed each day, for a total of over 15,000 every year.

Regulating insulin levels is essential for diabetes management. The current conventional therapy emphasizes the supplementation of the body’s insulin, usually by injections or external insulin pumps. This necessitates the patient to monitor blood glucose levels many times day and carefully regulate blood insulin levels. Although this is known as the optimal standard of treatment at now, researchers aim to discover methods to enhance the body’s production or regulation of its own insulin levels.

A 25-year-old woman with type 1 diabetes became the first person to successfully receive a transplant of insulin-producing cells derived from her own reprogrammed stem cells [1]. Less than three months after the transplant, she began producing her own insulin and has been free from insulin injections for over a year. She now enjoys eating foods she couldn’t before, such as sugar and hotpot.

This groundbreaking procedure, reported in Nature, marks a major step forward in diabetes treatment. James Shapiro, a transplant surgeon, said the surgery has completely reversed her diabetes, which previously required significant insulin doses [2].

A similar success occurred in Shanghai, where a 59-year-old man with type 2 diabetes received insulin-producing islets made from his own stem cells. He also no longer needs insulin. These pioneering studies demonstrate the potential of stem cells as a treatment for diabetes, offering a limitless supply of tissue and reducing the need for donor organs and immune-suppressing drugs.

In a groundbreaking trial, Deng Hongkui, a cell biologist at Peking University, and his team took cells from three people with type 1 diabetes and reverted them to a pluripotent state, meaning they could develop into any type of cell. This technique, originally developed by Shinya Yamanaka at Kyoto University nearly 20 years ago, was modified by Deng’s team to use small molecules instead of proteins, allowing for better control [3].

They used these chemically reprogrammed stem cells to create 3D clusters of insulin-producing islets, which were tested for safety in animals. In June 2023, the team transplanted about 1.5 million islets into a woman’s abdominal muscles—a new approach, as most islet transplants are done in the liver. By placing the cells in the abdomen, they could monitor them with MRI and remove them if necessary. The operation took less than 30 min.

Two and a half months after her transplant, the woman with type 1 diabetes started producing enough insulin on her own, and she has continued to do so for over a year. Her blood sugar levels are stable 98% of the time, eliminating dangerous spikes and drops. Daisuke Yabe, a diabetes researcher, called the results “remarkable” and hopes this approach can help more patients.

However, Jay Skyler, an expert in diabetes, stresses that more people need to be tested, and it will take up to five years of consistent insulin production to consider her fully cured.

Deng Hongkui, said the other two participants in the trial are also doing well, and he plans to expand the research. Since the woman was already taking immunosuppressants due to a previous liver transplant, the team couldn’t assess whether her body would reject the new cells. Although there was no sign of an autoimmune attack, they are working on ways to protect the cells from this risk, which is common in type 1 diabetes.

Transplants using a person’s own cells have benefits, but they are hard to scale and commercialize. To address this, several research groups have started trials using donor stem cells to create islet cells for treating diabetes.

In June, a trial led by Vertex Pharmaceuticals reported promising early results. A dozen people with type 1 diabetes received islet cells made from donated embryonic stem cells, injected into their livers. After three months, all participants began producing insulin, and some no longer needed insulin injections.

Vertex also started a new trial where islet cells are placed in a device that protects them from immune attacks, without the need for immunosuppressants.

Another trial, led by Daisuke Yabe, he plans to transplant sheets of islet cells made from donor stem cells into three people with type 1 diabetes. These participants will receive immunosuppressants, and the first transplant is scheduled for early upcoming year.

A Brazilian clinical trial involving 21 adults with type 1 diabetes showed that a stem cell infusion could help manage the disease, at least for several years. The study found that most patients were insulin-free for about three and a half years, with one patient going without insulin for eight years. Bart Roep, a diabetes expert, noted that this trial demonstrated the potential of stem cell transplants to treat diabetes. However, the treatment didn’t work for everyone, as some patients saw little to no improvement in their condition.

VX-880 is an experimental stem cell-derived therapy being tested in a phase 1/2 clinical trial for people with type 1 diabetes (T1D) who struggle with severe hypoglycemia and have impaired hypoglycemic awareness. The trial has been divided into following points: [4]

• Two patients received half the target dose. Both showed restored insulin production and better glucose control, and one patient no longer needed insulin injections.

• Five patients are receiving the full target dose. All have been treated, and data is being collected.

• Ten patients will receive the full dose concurrently.

The results so far are promising, showing that this treatment can restore insulin production and control blood sugar, potentially allowing patients to become insulin-independent. The treatment’s safety profile aligns with the immunosuppressive drugs used during the study.

All data will be provided in manuscript file.

The author acknowledges the college management, principal, teachers, non-teaching staff, and colleagues for their kind support.

No funding agency is acknowledged.

Authors and Affiliations

1. School of Pharmacy, Desh Bhagat University, Mandi Gobindgarh, Punjab, India

   Dinesh Kumar & Rajni Tanwar

Contributions

All authors have equal contributions.

Corresponding author

Correspondence to Dinesh Kumar.

Ethics approval and consent to participate

In this letter to the editor clinical phase study discussed

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I hereby give my consent for the publication of entitled “World’s First: Stem Cell Therapy Reverses Diabetes” in Stem Cell Research & Therapy.

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