Stem Cell Therapy to Reverse T1D Inspires Hope

During Diabetes Awareness Month, T1D Strong features articles to encourage, enlighten and embolden us to press forward with a disease that can be heavy-hearted to manage at times.

Last month, I received several emails, calls and texts from friends and neighbors about a 25-year-old woman in China whose type 1 diabetes (T1D) was ‘cured’ using stem cells. As a T1D mom, fifteen years after my son’s diagnosis at age four, I took this news with a dose of positive skepticism.

The older we get, the harder it is to fight that gnawing cynicism that tends to creep into our minds, especially when it comes to something as life-changing as a cure. But it’s important to stay focused and keep our hearts and minds open to possibilities, especially in the world of T1D research.

Insulin is not a cure, and immunosuppressant drugs and Ozempic are not cures. The Juvenile Diabetes Cure Alliance describes a practical cure for type 1 diabetes as a treatment that would free people from the daily management of the condition.

And though the recent clinical trial is a viable milestone and exciting achievement for reasons you’ll see below, it’s not exactly a T1D reversal for all.

Here’s the Facts

A 25-year-old woman with established T1D (she's had it for 11 years at the time of the trial) is now insulin-independent one year after stem cell therapy.

The clinical trial, which took place at Tianjin First Center Hospital in Tianjin, China, used chemically induced pluripotent stem cells (CiPSCs) taken from the woman’s body. The study, which claimed to be the first of its kind, transplanted the cells into the patient’s abdominal muscle.

Researchers published this advancement in the scientific journal Cell on September 25, 2024. The study reported that the woman sustained insulin independence starting 75 days post-transplantation.

Using her own cells, the doctors were able to avoid immune system rejection, leaving the patient insulin-independent and sustained insulin independence through the one-year assessment. Her time in range increased from 45% to 98%, and her HbA1c decreased from 7.57% to 5.37% at day 120.

However, the patient was on immunosuppressants throughout the trial due to previous liver transplants, which required a permanent regimen of immunosuppressive drugs. Which in addition to protecting her transplanted organs, she also protected the new islets from the patient’s autoimmune attack.

Additionally, the continued use of immunosuppressant drugs is required moving forward. Though immunosuppressant medications are effective at keeping beta cells alive for some, they aren’t ideal for everyone.

Immunosuppressant Side Effects

While immunotherapy is a treatment that activates the immune system, immunosuppressants make the immune system less active. Immunosuppressants can make patients vulnerable to an increased risk of infections and cancer.

Other Side Effects:

• Gastrointestinal issues: Side effects include upset stomach, abdominal pain, nausea, and vomiting. 
• Skin issues: Side effects include acne and mouth sores. 
• Hair issues: Side effects include hair loss or growth. 
• Headaches: Headaches are a common side effect. 

• High blood pressure: The drugs can increase the risk of high blood pressure. 
• High cholesterol: Immunosuppressants can increase the risk of high cholesterol. 
• Thinning bones: Immunosuppressants can increase your risk of osteoporosis. 
• Tremors: Immunosuppressants can cause tremors and shaking. 

Until there is a safe treatment without the use of immunosuppressants, we’re still searching for that practical cure.

Regarding this clinical trial, The Lancet reported, “Stem-cell transplantation would avoid the continuing issues of insufficient donors, but the possible methods to circumvent an autoimmune response from the recipient are still being investigated. The use of embryonic stem cell-derived islets requires lifelong immunosuppression, and while the use of allogeneic stem cells can avoid allograft rejection, the autoimmune process leading to the initial loss of endogenous insulin-producing cells will recur with the graft if not managed appropriately.”

Another important fact that some of the recent headlines failed to mention was that there were only three test subjects, and the results of the other two remain unknown.

However, a positive takeaway was that the clinical study used the abdominal muscle, which hasn’t been used previously, as most studies use the liver and omentum, a fold of fat below the stomach. The implantation site is essential, as the cells need adequate blood and oxygen to survive.

The Use of Stem Cells

Stem cell treatment is more commonly used to treat macular degeneration, blood cancers, and metabolic disorders. It’s exciting to see the science applied to diabetes as a promising therapeutic option.

In the case of the 25-year-old, embryonic stem/induced pluripotent stem (ES/iPS)- derived β cells were used. These cells are being developed as a new cell source for islet transplantation, and though they require immunosuppressant drugs, the hope is that they won’t in the future.

The Lancet also noted that Pluripotent stem cells from embryos caused significant ethical, political, and religious controversies. With the exciting recent developments in stem-cell therapy for diabetes, it is the duty of experts, scientists, and the media to ensure transparency with these advances.

One benefit of the above study is that the patient is not dependent on external cell supplies, which is the case in some donated cadaverous islets. And though these embryonic stem cells can be replicated, they might also be targeted by the patient’s immune system again.

Other Kinds of Stem Cell Therapy

More promising research possibilities include islet transplantation from donor pancreases into patients, porcine islet cells (from pigs), lab-grown islet cells and cells from patient’s bone marrow.

Likewise, here are some promising gene editing techniques for T1D beta cells.

Gene Editing

Though the above trial does not use gene-editing techniques, there are several in the works for T1D cells that aim to reprogram the body’s DNA. One gene therapy technique involves modifying the attacked beta cells by replacing the damaged genes with new modified ones.

Here are some companies working on gene-editing techniques right now:

CRISPR Therapeutics and ViaCyte

Both companies are collaborating to create islet cells that can escape an autoimmune response. In June 2022, they administered the first patient dose in a Phase I clinical trial of their gene-edited cell replacement therapy, VCTX210. 

CRISPR/Cas9

Here, scientists target and edit specific genes, cutting out mutated DNA and inserting corrected sequences more precisely.

Vertex

Vertex is developing gene-edited stem cell therapy where the stem cell-derived beta cells can potentially improve the time range to more than 99% in someone with T1D. 

Sana Biotechnology

 Sana Biotechnology is developing a gene editing technique that involves inserting genes that express “checkpoint” proteins to control the cells that destroy infected and diseased cells.

Why It’s Still Inspiring

If there were a way to protect the transplanted cells without immunosuppression drugs, which is the case with encapsulation, the clinical study would be more reciprocated by the T1D community. Also, if the study demonstrated a group larger than three individuals for a more extended time period.

Each company, T1D Strong spotlights (Diatech Diabetes, Diamyd Medical, and DiabeticU, to name a few), all strive to help T1Ds on the arduous journey of managing T1D through technology advancements that produce tighter time-in-range and lowered A1c levels. While all T1D research studies pave the way for new methodology in finding a cure, we remain hopeful.