Potential use of mesenchymal stem cells in the treatment of inflammatory bowel disease – a systematic review of the literature
Authors:
M. Lengálová 1; O. Ryska 2; A. Tremerová 1; P. Zusková 1; Z. Šerclová 1
Authors‘ workplace:
Chirurgické oddělení NH Hospital, a. s., Hořovice
1; Royal Lancaster Infirmary, University Hospitals of Mocerambe Bay NHS Foundation Trust, Lancaster, UK
2
Published in:
Rozhl. Chir., 2022, roč. 101, č. 4, s. 154-162.
Category:
Review
doi:
https://doi.org/10.33699/PIS.2022.101.4.154–162
Overview
Introduction: The incidence of inflammatory bowel disease is increasing worldwide and, despite advances in conservative and surgical treatment, a significant proportion of patients do not achieve complete remission and have to undergo repeated surgical procedures. Stem cell therapy is a new alternative to immunomodulatory therapy.
Methods: We performed a systematic review of the literature dealing with the use of mesenchymal stem cells for the treatment of IBD. The PubMed database was searched and original studies published between 2015 and 2021 were included.
Results: A total of 80 citations were found, of which 21 clinical studies and 47 experimental studies were included in the review.
Conclusion: The efficacy of MSCs in the treatment of perianal Crohn‘s disease is at least comparable to current therapies. A positive effect of MSC administration has also been demonstrated in animal models of luminal disease or enterocutaneous fistula. The results after systemic administration in IBD patients are still ambiguous. Key words: inflammatory bowel disease,
Keywords:
inflammatory bowel disease – mesenchymal stem cells – treatment – fistula
Sources
1. Lukáš K, Hoch J, a kol. Nemoci střev Praha, Grada Publishing 2018.
2. Jarkovský J, Benešová K, Hejduk K, et al. Epidemiology, hospitalization and migration of patients with IBD under specialized care in the Czech Republic. Gastroenterologie a hepatologie 2017;71(6):501–509. doi:10.14735/ amgh2017501.
3. Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol. 2020 Jan;145(1):16−27. doi:10.1016/j. jaci.2019.11.003.
4. MacDonald TT, Monteleone I, Fantini MC, et al. Regulation of homeostasis and inflammation in the intestine. Gastroenterology 2011;140(6):1768–1775 doi:10.1053/j.gastro.2011.02.047.
5. Li Ch, Juemmerle JF. Mechanisms that mediate the development of fibrosis in patients with Crohn‘s disease. Inflammatory Bowel Diseases 2014;20(7):1250–1258. doi:10.1097/MIB.0000000000000043.
6. Louis E, Collard A, Oger AF, et al. Behaviour of Crohn‘s disease according to the Vienna classification: changing pattern over the course of the disease. Gut 2001;49(6):777–782. doi:10.1136/ gut.49.6.777.
7. Frolkis AD, Dykeman J, Negrón ME, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population- based studies. Gastroenterology 2013;145(5):996–1006. doi:10.1053/j.gastro. 2013.07.041.
8. Dave M, Mehta K, Luther J, et al. Mesenchymal stem cell therapy for inflammatory bowel disease: A systematic review and meta-analysis. Inflammatory Bowel Diseases 2015;21(11):2696. doi:10.1097/ MIB.0000000000000543.
9. Chinnadurai R, Ng S, Velu V, et al. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease. WJG 2015;21(16):4779– 4787 doi:10.3748/wjg.v21.i16.4779.
10. Li Y, Ma K, Zhang L, et al. Human umbilical cord blood derived-mesenchymal stem cells alleviate dextran sulfate sodium- induced colitis by increasing regulatory T cells in mice. Front Cell Dev Biol. 2020 Nov 24;8:604021. doi:10.3389/ fcell.2020.604021.
11. Chao K, Zhang S, Qiu Y, et al. Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells. Stem Cell Research & Therapy 2016;7(1):109. doi:10.1186/s13287-016-0376-2.
12. Randhawa PK, Singh K, Singh N, et al. A review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol. 2014 Aug;18(4):279−288. doi:10.4196/ kjpp.2014.18.4.279. Epub 2014 Aug 13. PMID: 25177159; PMCID: PMC4146629.
13. Martín Arranz E, Martín Arranz MD, Robredo T, et al. Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis. Stem Cell Research & Therapy 1915;9(1):95. doi:10.1186/s13287-018-0837-x.
14. Stavely R, Robinson AM, Miller S, et al. Allogeneic guinea pig mesenchymal stem cells ameliorate neurological changes in experimental colitis. Stem Cell Res Ther. 2015 Dec 30;6:263. doi:10.1186/s13287- 015-0254-3.
15. Lian L, Huang Q, Zhang L, et al. Anti-fibrogenic potential of mesenchymal stromal cells in treating fibrosis in Crohn’s disease. Digestive Diseases and Sciences 2018;63(7):1821–1834. doi:10.1007/ s10620-018-5082-8.
16. Xu J, Wang X, Chen J, et al. Embryonic stem cell-derived mesenchymal stem cells promote colon epithelial integrity and regeneration by elevating circulating IGF-1 in colitis mice. Theranostics 2020;10(26):12204–12222. doi:10.7150/ thno.47683.
17. Barnhoorn M, de Jonge-Muller E, Molendijk I, et al. Endoscopic administration of mesenchymal stromal cells reduces inflammation in experimental colitis. Inflamm Bowel Dis. 2018 Jul 12;24(8):1755– 1767. doi:10.1093/ibd/izy130.
18. Hou H, Zhang L, Duan L, et al. Spatio-temporal metabolokinetics and efficacy of human placenta-derived mesenchymal stem/stromal cells on mice with refractory Crohn’s-like enterocutaneous fistula. Stem Cell Reviews and Reports 2020;16(6):1292–1304. doi:10.1007/ s12015-020-10053-2.
19. Soontararak S, Chow L, Johnson V, et al. Mesenchymal stem cells (MSC) derived from induced pluripotent stem cells (IPSC) equivalent to adipose-derived MSC in promoting intestinal healing and microbiome normalization in mouse inflammatory bowel disease model. Stem Cells Translational Medicine 2018;7(6):456–467. doi:10.1002/sctm.17- 0305.
20. Park JS, Yi TG, Park JM, et al. Therapeutic effects of mouse bone marrow-derived clonal mesenchymal stem cells in a mouse model of inflammatory bowel disease. J Clin Biochem Nutr. 2015 Nov;57(3):192−203 doi:10.3164/jcbn.15- 56.
21. Sala E, Genua M, Petti L, et al. Mesenchymal stem cells reduce colitis in mice via release of TSG6 independently of their localization to the intestine. Gastroenterology 2015 Jul;149(1):163−176.e20. doi:10.1053/j.gastro.2015.03.013.
22. Heidari N, Abbasi-Kenarsari H, Namaki S, et al. Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction. J Cell Physiol. 2021 Aug;236(8):5906−5920. doi:10.1002/jcp.30275.
23. Panés J, García-Olmo D, Assche GV, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology 2018 Apr;154(5):1334−1342.e4. doi:10.1053/j. gastro.2017.12.020.
24. Dietz AB, Dozois EJ, Fletcher JG, et al. Autologous mesenchymal stem cells, applied in a bioabsorbable matrix, for treatment of perianal fistulas in patients with Crohn’s disease. Gastroenterology 2017 Jul;153(1):59−62.e2. doi:10.1053/j. gastro.2017.04.001.
25. Dige A, Hougaard HT, Agnholt J, et al. Efficacy of injection of freshly collected autologous adipose tissue into perianal fistulas in patients with Crohn’s disease. Gastroenterology 2019;156(8):2208−2216.e1. doi:10.1053/j. gastro.2019.02.005.
26. Laureti S, Gionchetti P, Cappelli A, et al. Refractory complex Crohn’s perianal fistulas: A role for autologous microfragmented adipose tissue injection. Inflamm Bowel Dis. 2020 Jan 6;26(2):321–330, doi:10.1093/ibd/izz051.
27. Barnhoorn MC, Wasser MNJM, Roelofs H, et al. Long-term evaluation of allogeneic bone marrow-derived mesenchymal stromal cell therapy for Crohn’s disease perianal fistulas. J Crohns Colitis 2020 Jan 1;14(1):64–70. doi:10.1093/ecco-jcc/ jjz116.
28. Ciccocioppo R, Gallia A, Sgarella A, et al. Long-term follow-up of Crohn disease fistulas after local injections of bone marrow– derived mesenchymal stem cells. Mayo Clin Proc. 2015 Jun;90(6):747–755. doi:10.1016/j.mayocp.2015.03.023.
29. Herreros MD, Garcia-Olmo D, Guadalajara H, et al. Stem cell therapy: A compassionate use program in perianal fistula. Stem Cells Int. 2019 May 5;2019:6132340. doi:10.1155/2019/6132340.
30. Park KJ, Ryoo SB, Kim JS, et al. Allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn‘s disease: a pilot clinical trial. Colorectal Disease 2016;18(5):468–476. doi:10.1111/ codi.13223.
31. Zhou Ch, Li M, Zhang Y, et al. Autologous adipose-derived stem cells for the treatment of Crohn’s fistula-in-ano: an open-label, controlled trial. Stem Cell Research & Therapy 2020. doi:10.1186/ s13287-020-01636-4.
32. Cho YB, Park KJ, Yoon SN, et al. Longterm results of adipose-derived stem cell therapy for the treatment of Crohn‘s fistula. Stem Cells Transl Med. 2015 May;4(5):532−537. doi:10.5966/ sctm.2014-0199.
33. Wainstein C, Quera R, Fluxá D, et al. Stem cell therapy in refractory perineal Crohn‘s disease: long-term follow-up. Colorectal Disease 2018. doi:10.1111/ codi.14002.
34. Šerclová Z, Ryska O, Bortlík M, et al. Eradikace perianálních píštělí u IBD nemocných pomocí metody Advancement Flap a rizikové faktory neúspěšného hojení. Gastroenterologie a hepatologie 2015;69(1):25–28. doi:10.14735/ amgh201512.
35. Nikolic M, Stift A, Reinisch W, et al. Allogeneic expanded adipose-derived stem cells in the treatment of rectovaginal fistulas in Crohn’s disease. Colorectal Disease 2021;23(1):153–158. doi. org/10.1111/codi.15324.
36. García-Arranz M, Herreros MD, González-Gómez C, et al. Treatment of Crohn‘s‐related rectovaginal fistula with allogeneic expanded‐adipose derived stem cells: A phase I–IIa clinical trial. Stem Cells Translational Medicine 2016;5(11):1441–1446. doi:10.5966/ sctm.2015-0356.
37. Lightner AL, Dozois EJ, Dietz AB, et al. Matrix-delivered autologous mesenchymal stem cell therapy for refractory rectovaginal Crohn’s fistulas. Inflammatory Bowel Diseases 2020;26(5):670–677. doi:10.1093/ibd/izz215.
38. da Costa Gonçalves F, Grings M, Schneider Nunes N, et al. Antioxidant properties of mesenchymal stem cells against oxidative stress in a murine model of colitis. Biotechnol Lett. 2017 Apr;39(4):613−622. doi:10.1007/s10529-016-2272-3.
39. Zheng XB, He XW, Zhang LJ, et al. Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice. Gastroenterol Rep (Oxf) 2019 Apr;7(2):127−138. doi:10.1093/gastro/goy017.
40. Lopez-Santalla M, Hervas-Salcedo R, Fernandez-Garcia M, et al. Cell therapy with mesenchymal stem cells induces an innate immune memory response that attenuates experimental colitis in the long term. Journal of Crohn’s and Colitis 2020;14(10):1424–1435. doi:10.1093/ecco- jcc/jjaa079.
41. Kawata Y, Tsuchiya A, Seino S, et al. Early injection of human adipose tissue- derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells. Cell and Tissue Research 2019;376(2):257–271. doi:10.1007/s00441-018-02981-w.
42. Ikarashi S, Tsuchiya A, Kawata Y, et al. Effects of human adipose tissue-derived and umbilical cord tissue-derived mesenchymal stem cells in a dextran sulfate sodium-induced mouse model. BioResearch Open Access 2019;8,(1):185–199. doi:10.1089/biores.2019.0022.
43. Liu H, Liang Z, Wang F, et al. Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism. JCI Insight. 2019 Dec 19;4(24):e131273. doi:10.1172/jci.insight.131273.
44. Nishikawa T, Maeda K, Nakamura M, et al. Filtrated adipose tissue-derived mesenchymal stem cell lysate ameliorates experimental acute colitis in mice. Digestive Diseases and Sciences 2021;66(4): 1034– 1044. doi:10.1007/s10620-020-06359-3.
45. Regmi S, Seo Y, Ahn JS, et al. Heterospheroid formation improves therapeutic efficacy of mesenchymal stem cells in murine colitis through immunomodulation and epithelial regeneration. Biomaterials 2021;271:120752. doi:10.1016/j.biomaterials. 2021.120752.
46. Stavely R, Robinson AM, Miller S, et al. Human adult stem cells derived from adipose tissue and bone marrow attenuate enteric neuropathy in the guinea-pig model of acute colitis. Stem Cell Research & Therapy 2015;6(1):244. doi:10.1186/ s13287-015-0231-x.
47. Dorian Forte, et al. Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn’s disease patients in a mouse model of colitis. Stem Cell Research & Therapy 2015;6(1)5):170. doi:10.1186/ s13287-015-0166-2.
48. Yang H, Feng R, Fuet Q, et al. Human induced pluripotent stem cell-derived mesenchymal stem cells promote healing via TNF-α-stimulated gene-6 in inflammatory bowel disease models. Cell Death & Disease 2019;10(10):1–16. doi:10.1038/ s41419-019-1957-7.
49. Yang R, Huang H, Cui S, et al. IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via MiR- 125a and MiR-125b. Cell Death & Disease 2020;11(7):1–12. doi:10.1038/s41419- 020-02788-0.
50. Cao X, Duan L, Hou H, et al. IGF-1C hydrogel improves the therapeutic effects of MSCs on colitis in mice through PGE2-mediated M2 macrophage polarization. Theranostics 2020;10(17):7697– 7709. doi:10.7150/thno.45434.
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