Mesenchymal Stem Cells for the treatment of Crohn’s disease
Crohn’s disease (CD) is an inflammatory bowel disease involving chronic inflammation of any part of the gastrointestinal tract. The disease incidence is on the rise across the globe with the exact cause behind still being explored by research. There is a wide range of factors involved ranging from genetics to changes in the gut bacteria (microbiota) to an aberrant immune system and environmental factors. The inflammation in CD can be anywhere along the gastrointestinal tract with symptoms described as chronic and relapsing. Patients are administered recurrent operations and immunosuppression that however, are not able to cure the condition. The complexity of the disease necessitates looking at other treatment options especially, personalized approaches (Roda and team, 2020).
Given the advantages of mesenchymal stem cells (MSCs) in terms of the ability to differentiate, availability from many tissues, limited ethical challenges, and their ability to modulate the immune system, research has reported encouraging results to use Mesenchymal Stem Cells for the treatment of Crohn’s disease (CD).
The safety and feasibility of using autologous bone marrow-derived mesenchymal stromal cells to treat patients suffering from Crohn’s disease with external fistulas were reported in 2011 by scientists Ciccocioppo and team. 10 patients received Bone marrow MSCs intrafistular MSC injections every 4 weeks. While the disease index was lowered in all patients, 7 patients showed complete closure while 3 showed incomplete closure of fistula tracks. While no adverse effects were reported, an increase in mucosal and circulating regulatory T cells was also observed, showing the safety and efficacy of mesenchymal stem cells for Crohn’s disease (CD).
The healing effects of bone marrow MSCs was shown in a double-blind, placebo-controlled study (ClinicalTrials.gov ID NCT01144962). Molendijk and team (2015) observed that 85.7% of the patients with perianal fistulizing Crohn’s disease healed with the administration of MSCs against 22.2% in the placebo group. This becomes significant given that perianal CD (affecting 1/4th of the CD patients) is a huge challenge to treat with medicines or surgery. A further challenge is the refractory nature of the disease in 37% of patients! This leads to a cycle of surgery and immunosuppression: both with side effects such as incontinence for the former and opportunistic infection due to the latter. Overall, there is an affected quality of life and significant costs incurred due to the condition. Thus, MSCs show the way ahead for treating this condition.
Scientists Panes and team (2018) showed the long-term safety and efficacy of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn’s disease and perianal fistulas in a randomized placebo-controlled trial (ClinicalTrials.gov no: NCT01541579). 50% of 212 patients with Crohn’s disease received the stem cells while the others received a placebo along with standard care. 100% closure of baseline fistulas was seen in 60% of the patients who received MSCs plus the standard treatment at week 52 (one year).
The challenges associated with Crohn’s disease are numerous affecting the lives of thousands of patients across the globe. The need of the hour is healing-that is shown by the use of MSCs. The magic of mesenchymal stem cells is here to stay.
Roda, G., Chien Ng, S., Kotze, P.G. et al. Crohn’s disease. Nat Rev Dis Primers 6, 22 (2020). https://doi.org/10.1038/s41572-020-0156-2
Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease. Gut. 2011;60(6):788-798. doi:10.1136/gut.2010.214841
Molendijk I, Bonsing BA, Roelofs H, et al. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn’s Disease. Gastroenterology. 2015;149(4):918-27.e6. doi:10.1053/j.gastro.2015.06.014
Panés J, García-Olmo D, Van Assche G, et al. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn’s Disease. Gastroenterology. 2018;154(5):1334-1342.e4. doi:10.1053/j.gastro.2017.12.020
Carvello, M., Lightner, A., Yamamoto, T., Kotze, P. G., & Spinelli, A. (2019). Mesenchymal Stem Cells for Perianal Crohn’s Disease. Cells, 8(7), 764. https://doi.org/10.3390/cells8070764