How Stem Cell Therapy Can Support Inflammatory Bowel Disease

Gastrointestinal issues are on the rise, affecting 60-70 million people in the United States alone.¹ These range from mild discomfort to chronic conditions like Inflammatory Bowel Disease (IBD). With the rise of heavily processed foods and takeout making cooking easy, it’s no wonder this is the case. These tend to be heavy in saturated fats, sugars, and synthetic additives that cause inflammation in our bodies.

For many people, these issues are rooted in persistent inflammation and damage to the digestive tract, leading to significant impacts on daily life. While dietary changes and conventional treatments can help manage symptoms, emerging therapies are exploring other ways to heal the root causes of IBD. Among these is stem cell therapy—particularly mesenchymal stem cells (MSCs), which can repair damaged tissues, reduce inflammation, and offer new hope for IBD patients.

What is IBD

IBD is a set of conditions that affects the intestinal tract. It’s characterized by chronic and ongoing inflammation that can damage both small and large intestines. It’s a global health issue that’s been on the rise, impacting between 2.4 and 3.1 million Americans.

While the cause of IBD is still unclear, research suggests it involves a combination of genetic, environmental, immune, and microbial factors.² There are over 240 genes connected to IBD with NOD2, ATG16L, and CARD9 being the most relevant. Each of these genes helps support the immune system, and mutations to them can lead to an overactive or poorly functioning immune system. These can explain the autoimmune characteristics of IBD, in that the body may start to attack its own gut cells incorrectly because of these mutations and gene malfunctions.

Environmental factors like stress and poor diet can also play a role in IBD. These not only can affect how certain genes are turned on or off, known as epigenetics, but can also affect your gut microbiome. Having imbalances in gut bacteria, known as dysbiosis, can decrease the levels of healthy bacteria in your gut, leading to higher levels of inflammation in the gut.

There are two main classifications of IBD, and while they are often lumped together, there are some distinguishing differences:³

Crohn’s disease (CD)

In CD, inflammation can occur anywhere along the GI tract, from the mouth to the anus. Inflammation may occur in patches or in multiple GI organs. For example, there may be healthy parts of the colon between diseased sections. Granulomas are lesions formed by clumped inflamed cells only present in CD, and pain is typically felt on the lower right side of the abdomen.

Ulcerative colitis (UC)

UC typically only affects the colon, though in rare cases, parts of the small intestine closest to the colon (Ileum) also have inflammation. Unlike CD, inflammation is continuous, often starting at the rectum or sigmoid colon and moving up through the colon as the disease spreads. There is more bleeding associated with UC, and pain is typically in the lower left side of the abdomen.

Diagnosis for both conditions involves a series of tests, including endoscopy (camera into the stomach) and colonoscopy (camera into the colon), as well as blood work and other imaging.

Current treatments

The most common treatments for IBD are medications and surgery, depending on the severity of the disease. Medications for CD and UC are similar, though some may be more effective for one disease or the other.

There are several current treatment options for UC and CD: ⁴

• Anti-inflammatory medications are the go-to treatment for IBD. They target inflammation in the intestinal lining, which helps symptoms like diarrhea, abdominal pain, and rectal bleeding.
• Corticosteroids, like prednisone, are strong anti-inflammatories used in more severe cases of IBD. Though they help control symptoms quickly, they are not recommended for long-term use.
• Immunosuppressants work by suppressing the immune system to reduce inflammation and symptom flare-ups.
• Biologic therapies are newer approaches that target specific parts of the immune system to help reduce inflammation and reduce immune overreactivity.⁵

The major drawback of these medications is that they only treat the symptoms and do not tackle the underlying cause of the disease, which is immune system dysfunction. With the increasing rates of IBD, there is a growing need for a treatment that targets these root causes, which is where stem cells come in.

Stem cells are emerging as promising as therapeutic agents because of their ability to repair and replace damaged cells, and influence the immune system. Mesenchymal stem cells (MSCs), specifically, have potent immune functions, making them particularly interesting for treating inflammatory bowel disease (IBD).

What are MSCs

Mesenchymal stem cells (MSCs) are a specific type of stem cell known for their ability to turn into various cell types. This makes them a crucial player in cell repair and healing in the field of regenerative medicine. These versatile cells have gained attention due to their potential to repair and regenerate damaged tissues, offering hope for treating various conditions, including orthopedic injuries, cardiovascular diseases, and autoimmune disorders, and many more.⁶

At their core, mesenchymal stem cells are a unique subset of stem cells that originate from the mesoderm, one of the three primary germ layers in early embryonic development. Unlike embryonic stem cells, which have the potential to develop into any cell type in the body, MSCs are multipotent. This means they can transform into several specific cell types, including bone cells (osteoblasts), cartilage cells (chondrocytes), nerve cells (neurons), and fat cells (adipocytes), among others. This adaptability makes them invaluable for tissue engineering and regenerative therapies.⁷

In addition to their differentiation capabilities, MSCs are also known for their positive impact on the immune system. They can help regulate the immune response, making them useful in treating inflammatory conditions. Moreover, they secrete various growth factors and cytokines that stimulate tissue repair, further enhancing their therapeutic potential.

The science of UC-MSCs and IBD

More and more research is exploring the benefits of MSCs as a therapy for IBD.

In general, stem cell therapy has shown to support IBD by regulating an over active immune system. They can interact with a variety of immune cells including T-cells, macrophages, and dendritic cells that help promote anti-inflammation and maintain immune tolerance and can even reprogram immune cells to become anti-inflammatory. MSCs have proven to be able promote intestinal cell repair and prompting new blood cells which is critical for bring oxygen and nutrients to regenerate damaged tissue. Clinically, MSCs have shown promise in reducing the number of bowel movements, inflammation, rectal bleeding and abdominal pain.⁸

Two types of stem cells are typically used to treat IBD: Hematopoietic stem cells (HSCs) and MSCs. While HSCs can help some patients who don’t respond to conventional treatments, they involve intensive procedures that carry high risks of infection, rejection, and rate of relapse. MSCs are much more accessible and are more universal, so they are also easier to use. They have low immunogenicity, meaning they are not likely to trigger an immune response and can be used safely in many different contexts. Recently researchers have investigated intestinal stem cells (ISCs), which become various types of intestinal cells helping to repair damaged tissue and regulate immune cells in the intestinal tract. These are an exciting new prospect as they can be turned into organoids, which are the best sources of stem cells for IBD.⁹

In UC specifically, MSCs have shown promise in clinical settings. A study just published this month looked at the safety and efficacy of UC-MSCs as a therapeutic agent for UC. They enrolled 41 patients with UC who didn’t respond to conventional medications. Participants were given monthly UC-MSCs intravenously (IV) for two months. After two months of UC-MSC treatment, 73.2% of patients showed a clinical response, a significant improvement in symptoms, and 41.5% achieved clinical remission, where their symptoms were almost completely gone. After six months, 61% maintained a clinical response, and 34.2% were still in clinical remission. Levels of cytokines, key inflammatory proteins, were also significantly lower in patients given UC-MSCs, suggesting a reduction in inflammation.¹⁰

Research has also started to investigate the effects of MSCs specifically in CD due to their potent immune benefits and past research on other autoimmune conditions. Eighty-two patients with moderate to severe CD participated in a clinical trial comparing corticosteroid treatment to UC-MSCs therapy. Half of the participants were given four IV infusions, one per week. Twelve months after treatment, Crohn’s symptom severity decreased by 62.5 points in the treatment groups compared to only 23.6 points in the controls. Patients in the UC-MSC group were also able to reduce their corticosteroid dose by 4.2mg/day whereas the control group only reduced by 1.2mg/day.¹¹

To learn more about the process of how stem cells are delivered, check our article here

The takeaway

The growing rates of gastrointestinal issues, especially inflammatory bowel disease (IBD), highlights the need for more effective treatments that go beyond managing symptoms. While traditional therapies like corticosteroids and immunosuppressants help control flare-ups, they don’t address the underlying causes of chronic inflammation. MSC therapy, particularly with UC-MSCs, has emerged as a promising approach to changing the immune response and promoting tissue repair. As research continues to explore their potential, MSC therapies could pave the way for more targeted and sustainable solutions in the management of IBD.

Resources

1. https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases
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3. Fakhoury, M., Negrulj, R., Mooranian, A., & Al-Salami, H. (2014). Inflammatory bowel disease: clinical aspects and treatments. Journal of inflammation research, 7, 113–120. https://doi.org/10.2147/JIR.S65979
4. Seyedian, S. S., Nokhostin, F., & Malamir, M. D. (2019). A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. Journal of medicine and life, 12(2), 113–122. https://doi.org/10.25122/jml-2018-0075
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7. Stem Cells: Types, What They Are & What They Do. Cleveland Clinic. https://my.clevelandclinic.org/health/body/24892-stem-cells
8. Tian, C. M., Zhang, Y., Yang, M. F., Xu, H. M., Zhu, M. Z., Yao, J., Wang, L. S., Liang, Y. J., & Li, D. F. (2023). Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges. Journal of inflammation research, 16, 2089–2119. https://doi.org/10.2147/JIR.S400447
9. Tian, C. M., Zhang, Y., Yang, M. F., Xu, H. M., Zhu, M. Z., Yao, J., Wang, L. S., Liang, Y. J., & Li, D. F. (2023). Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges. Journal of inflammation research, 16, 2089–2119. https://doi.org/10.2147/JIR.S400447
10. Jiang, X., Luo, X., Cai, C., Bai, Y., Ding, H., Yue, H., Li, Y., Yang, Z., Zhang, H., Liang, Y., Peng, C., Huang, H., Liu, M., Li Z., Shi, Y., Han, S, Li, X. & Zhang, B. (2024). Umbilical cord mesenchymal stem cells in ulcerative colitis treatment: efficacy and possible mechanisms. Stem Cell Research & Therapy, 15(1), 272. https://doi.org/10.1186/s13287-024-03878-y
11. Zhang, J., Lv, S., Liu, X., Song, B., & Shi, L. (2018). Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial. Gut and liver, 12(1), 73–78. https://doi.org/10.5009/gnl17035