Inflammatory bowel disease (IBD) is a chronic, inflammatory disease of the bowel [1]. IBD is sub-classified as Crohn’s disease or ulcerative colitis, depending on the portion of the gastrointestinal tract afflicted [1]. As of 2015, the disease affects more than three million people in the United States alone, and its occurrence is increasing worldwide for reasons that are not well understood [2]. The disease can be debilitating and costs the United States $25 billion annually [3]. It is one of the most expensive gastrointestinal disorders in the world [3].
The exact cause of IBD is unknown, but it is likely multifactorial, involving dysregulation of the immune system, disruption of the intestinal mucosal barrier, and genetic factors [4]. In any case, the pathogenesis of IBD results in a dysfunctional intestine. Symptoms manifest as adverse gastrointestinal events, including bloody stools, diarrhea, and weight loss [5].
There is no cure for IBD. Medical treatment aims to reduce symptoms, prevent complications, and slow disease progression [6]. Therapy involves significant lifestyle changes and pharmacological agents [6]. Pharmacology includes immunosuppressive drugs, corticosteroids, and biological agents [7].
Current pharmacological agents for IBD can achieve remission for some patients, but they carry adverse side effects such as an increased risk of infection or cancer [8]. Moreover, a large subset of patients (approximately 30%) do not respond to conventional treatment [9]. Up to one quarter of Crohn’s patients may develop disabling, refractory complications like perianal fistulae, which can cause a lack of control over the bowels or sepsis [8].
Because IBD involves functional impairment of the intestinal barrier, regenerative medicine has been proposed to address the unmet medical needs of IBD patients. Regenerative medicine is a branch of medicine that regenerates functional tissue in patients who lack it, either due to injury or chronic disease [10]. Stem cell therapy is a component of regenerative medicine that holds promise for IBD.
Stem cells are cells that have not yet fully matured [11]. They are thus undifferentiated and can give rise to many different cell types in the body. Stem cell therapy transplants stem cells into diseased tissue with the aim that the stem cells give rise to functional, differentiated progeny, which then constitutes the new tissue. Stem cells can also inhibit inflammation and activate biochemical pathways that promote healing [12].
Stem cell therapy for IBD has focused on two types of stem cells: hematopoietic stem cells (HSCs), derived from adult peripheral blood and the bone marrow; and mesenchymal stem cells (MSCs), derived from adult bone marrow [12]. Stem cell research in IBD has made serious advancements, especially in the treatment of Crohn’s disease. Animal studies first showed that HSCs and MSCs could eliminate IBD genetic defects, reconstitute the immune system, and accelerate the repair of damaged intestinal mucosal tissues [12]. Clinical trials have since confirmed the efficacy of HSC and MSCs. In a phase three clinical trial study published in the Lancet, Panés et al. (2016) showed that MSCs are safe and effective in treatment-refractory Crohn’s disease with perianal fistulas, with more patients achieving remission after stem cell injection than placebo [13]. A 2021 systematic review from Wang et al. evaluated 46 studies of stem cells treating Crohn’s disease, including 18 human trials, reached similar conclusions. After analyzing the beneficial effects of stem cells on various parameters, including patient quality of life, remission rates, disease activity score, and mucosal healing, the authors asserted that “stem cell transplantation is a valuable supplementary therapy for [Crohn’s disease]”[12]. The review also found that HSCs worked better against Crohn’s disease than MSCs, and that cells taken from the patient carried fewer side effects than when cells were taken from a donor [12].
Although the effectiveness of stem cell therapy for IBD has been largely confirmed by clinical trials, safety concerns have been a major barrier in implementing stem cells in routine clinical practice. For example, Wang et al. reported that two patients died from cytomegalovirus infections from HSCT [12]. However, safety concerns have been mitigated by using strict hygiene procedures before and after surgery, antibiotic prophylaxis, and performing transplantations at technologically-advanced institutions [12]. Wang et al. concluded that the implementation of such measures in recent studies has dramatically improved safety [12].
Researchers are also using stem cells to create “mini guts” to treat and learn more about IBD [14]. Using the patient’s own cells, they can make a “gut in a dish” that resembles the patient’s gut. Then, they can test different therapies on the manufactured gut to personalize treatment to the patient’s unique intestinal environment. They can also perform experiments on the mini guts to learn more about the pathophysiology behind IBD.
In conclusion, stem cells are a promising new therapy for IBD, a disease that costs the United States billions of dollars and affects millions of lives. Safety concerns have been a barrier preventing stem cell therapy from entering traditional clinical practice. However, safety has improved with the implementation of new preventative practices. This is why at Eterna Health, we have partnered with pioneering scientists who ensure the highest quality control in the world to mitigate risk of infection. We are actively treating IBD patients using IV stem cells, fecal microbial transplant and peptides!
1. McDowell, C., U. Farooq, and M. Haseeb, Inflammatory Bowel Disease, in StatPearls. 2022: Treasure Island (FL).
2. Dahlhamer, J.M., et al., Prevalence of Inflammatory Bowel Disease Among Adults Aged >/=18 Years – United States, 2015. MMWR Morb Mortal Wkly Rep, 2016. 65(42): p. 1166-1169.
3. Singh, S., et al., Trends in U.S. Health Care Spending on Inflammatory Bowel Diseases, 1996-2016. Inflamm Bowel Dis, 2022. 28(3): p. 364-372.
4. Lee, S.H., J.E. Kwon, and M.L. Cho, Immunological pathogenesis of inflammatory bowel disease. Intest Res, 2018. 16(1): p. 26-42.
5. Perler, B.K., et al., Presenting symptoms in inflammatory bowel disease: descriptive analysis of a community-based inception cohort. BMC Gastroenterol, 2019. 19(1): p. 47.
6. Cai, Z., S. Wang, and J. Li, Treatment of Inflammatory Bowel Disease: A Comprehensive Review. Front Med (Lausanne), 2021. 8: p. 765474.
7. Zhang, H.M., et al., Stem Cell-Based Therapies for Inflammatory Bowel Disease. Int J Mol Sci, 2022. 23(15).
8. Ng, S.C. and A.N. Ananthakrishnan, New approaches along the IBD course: diet, tight control and stem cells. Nat Rev Gastroenterol Hepatol, 2019. 16(2): p. 82-84.
9. Hazel, K. and A. O’Connor, Emerging treatments for inflammatory bowel disease. Ther Adv Chronic Dis, 2020. 11: p. 2040622319899297.
10. Atala, A., Principles of regenerative medicine. 2nd ed. 2011, Amsterdam ; Boston: Elsevier, Academic Press. xix, 1182 p.
11. Zakrzewski, W., et al., Stem cells: past, present, and future. Stem Cell Res Ther, 2019. 10(1): p. 68.
12. Wang, R., et al., Stem cell therapy for Crohn’s disease: systematic review and meta-analysis of preclinical and clinical studies. Stem Cell Res Ther, 2021. 12(1): p. 463.
13. Panes, J., et al., Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet, 2016. 388(10051): p. 1281-90.
14. Li, V.S.W., Modelling intestinal inflammation and infection using ‘mini-gut’ organoids. Nat Rev Gastroenterol Hepatol, 2021. 18(2): p. 89-90.
