Can stem cell therapy cure diabetes?

Diabetes is quickly becoming one of the most urgent global public health crises. Currently, 540 million people worldwide have diabetes, and that number is projected to increase to 783 million by 2045. More than 90% of cases are type 2 diabetes, which includes insulin resistance and beta-cell dysfunction.  

Type 1 diabetes, also known as juvenile diabetes, is an autoimmune disorder where insulin-producing beta cells in the pancreas are destroyed, is also rising at alarming rates. In 2021, over 8 million people globally had type 1 diabetes, and that is expected to increase to as much as 17 million people by 2040.

When unmanaged, diabetes can lead to chronic complications affecting multiple systems, especially microvascular diseases such as retinopathy, nephropathy, and neuropathy, as well as macrovascular diseases including cardiovascular, cerebrovascular, and peripheral vascular diseases, all of which are associated with high morbidity and mortality. In 2021, diabetes and kidney disease due to diabetes caused over 2 million deaths globally, and around 11% of cardiovascular deaths were linked to high blood glucose.

What’s changing in diabetes research

The conventional approaches to managing both type 1 and type 2 diabetes include continuous monitoring of blood sugar levels and maintaining a healthy lifestyle. Type 1 diabetes patients must rely on insulin supplements in the form of daily injections, while type 2 patients use oral medications like metformin, sulfonylureas, and DPP-4 inhibitors.  

With the increasing prevalence of these diseases and the aging of the overall global population,more cases of type 2 diabetes are expected, showing a need for better treatment options. In 2022, the FDA approved teplizumab to delay the onset of type 1 diabetes, and newer drugs like GLP-1 receptor agonists and SGLT-2 inhibitors are being explored for type 2.  

However, more recent breakthroughs involve pancreatic islet cellular therapy to restore insulin secretion for patients with type 1 diabetes. The first successful attempts at differentiating stem cells into insulin-producing cells happened in the early 2000s, and clinical trials began in the 2010s. It was in 2023, however, that the FDA approved Lantidra, the first cellular therapy for type 1 diabetes patients. Recent studies also demonstrated the potential of stem cell-derived islet cells to restore insulin production in diabetes patients, reducing or even eliminating the need for external insulin injections.  

New strategies are being explored to enhance the success and longevity of stem cell therapy, and these approaches could result in more effective and long-lasting treatments for type 1 and type 2 diabetes. We examined the CAS Content Collection^TM, the largest human-curated repository of scientific information, and found a marked increase in publications relating to stem cell therapy for diabetes from 2000 to 2023.  

As seen in Figure 1, there are more publications relating to stem cell therapy and type 1 diabetes than type 2. Furthermore, for type 1, the journal articles contribute 58% and patents contribute 42% of the total documents. For type 2, the number of journal articles is higher at 82% while the number of patents is only 18%.

Types of stem cells showing potential for diabetes treatment

Stem cells are unspecialized cells capable of differentiating into various specialized cell types. There are three main types:

1. Adult stem cells: Multipotent cells found in tissues that can develop into a limited range of related cell types, such as hematopoietic stem cells (which can differentiate into various types of blood cells) and mesenchymal stem cells (which can differentiate into bone, cartilage, and fat cells).

2. Induced pluripotent stem cells (iPSCs): A type of pluripotent stem cell generated directly from adult (mature) somatic cells. These cells are reprogrammed back into an embryonic-like state, allowing them to differentiate into any cell type in the body.

3. Embryonic stem cells (ESCs): Pluripotent cells from early-stage embryos that can become almost any cell type.

We analyzed the types of stem cells being explored for diabetes treatments and found that, for type 1 and type 2 diabetes, adult stem cells are the most consistently researched (see Figure 2). Among adult stem cells, the most prominent type is mesenchymal stem cells (MSCs) followed by neural, hematopoietic, pancreatic, and cord blood stem cells.  

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The treatment candidate VX-880, derived from ESCs, is entering a phase III clinical trial (NCT04786262). VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy developed for the treatment of type 1 diabetes. There have been encouraging results with this candidate, and in November 2024, Vertex Pharmaceuticals announced the start of a pivotal phase III trial enrolling 50 patients. This demonstrates the potential of many stem cell types to not just treat, but even to cure, diabetes.

In our analysis of the CAS Content Collection, we noted the year-wise trend of published documents related to each stem cell type for type 1 and type 2 diabetes research (see Figure 3). For both types, initial studies investigated adult stem cells (mainly MSCs) and ESCs. However,  research on adult stem cells has grown compared to ESCs. Documents related to iPSCs also show steady growth for both types. Exosome-related documents or studies, which only started about a decade ago, are also on the rise.

Advantages and limitations of various stem cell types

• MSCs: These adult stem cells can be isolated from various sources (bone marrow, adipose tissue), and they have low immunogenicity since they lack MHC-II complex and exhibit lower expression of MHC-I complex. They can modulate immune responses and inflammation and are relatively safe for clinical use with fewer tumorigenic risks. However, they have limited differentiation potential when compared to pluripotent stem cells, and there can be inconsistent cell quality and potency across donors. It’s also difficult to maintain these in their stem cell state in vitro, which makes scalability difficult. Lastly, there can be ethical concerns if they’re derived from human donors.

• iPSCs: There are fewer ethical concerns with iPSCs since they are derived from somatic cells, and immune rejection can be avoided if they’re derived from the same patient. In terms of limitations, reprogramming these cells can be time-consuming, expensive, and challenging. There is also a risk of genetic mutations during the reprogramming process and high tumorigenic potential.

• ESCs: These exhibit high regenerative potential and are well-characterized and studied. They have high proliferation rates, which makes them suitable for large-scale production. They do, however, have a risk of teratoma formation, and there have been ethical concerns surrounding their use.

Each type of stem cell has been the subject of important research, which we summarize in Table 1:

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Table 1: Types of stem cells and findings from key studies.

Potential advances and challenges in stem cell treatments

It’s possible that stem cell therapies could be used to treat many of the complications that come with diabetes. Today, conventional diabetes treatment options focus on regulating blood glucose levels, but they’re not efficient in reducing or treating the complications that can accompany this disease.

For example, a recent meta-analysis showed that diabetic foot patients can benefit from stem cell therapy, as indicated by various parameters like healing rate, amputation rate, pain scores, and new angiogenesis rate. Other studies have attempted to understand the mechanisms and applications of stem cells in diabetic nephropathy and cardiovascular complications in diabetic patients.

Even though stem cells hold enormous potential in diabetes treatment, several challenges remain which may hinder their widespread application. One particular concern is immune rejection, especially if the cells are from another donor (an allogeneic source). Maintaining the viability and efficiency of transplanted stem cells is also a challenge, and there are risks of developing tumors. To address immunogenicity and teratogenesis after transplantation, scientists are using immune-isolation devices, encapsulation methods, or immunosuppressive therapies.

As researchers make progress on these challenges, it’s possible that we can develop not just treatments but cures for type 1 and type 2 diabetes. With these conditions becoming more prevalent, it is critical for the scientific community to keep making breakthroughs with innovative treatment options.