MSC therapy for inflammatory bowel disease

Cover Page

Cite item

Full Text

Abstract

Inflammatory bowel disease (IBD) belongs to the group of diseases characterized by idiopathic inflammation of the digestive tract organs. Two basic IBD types are distinguished: ulcerative colitis and Crohn’s disease. The IBD symptoms including vomiting and diarrhea, abdominal pain, rectal bleeding, anemia have a significant negative impact on the general patient’s state of health. Besides, IBD patients are susceptible to the risk of a number of serious diseases such as colorectal cancer, thrombosis and primary sclerosing cholangitis. More than 4 million people in the USA and Europe suffer from IBD, with 70000 new cases diagnosed yearly in the USA only.

In some cases, a surgical removal of the damaged digestive tract fragments is required to treat severe IBD forms. However, drug therapy of IBD has mainly been used in the last decades. The rate of remission with application of traditional IBD therapy is estimated as 20-30%, and is still no higher than 50% with the combined therapy. Cell therapy has been proven to be a very promising approach in the IBD treatment. In our review, we discuss mesenchymal stromal cells (MSC) and the most important preclinical and clinical results of their application for the IBD therapy.

About the authors

Mikhail A. Konoplyannikov

Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies FMBA of Russia; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: mkonopl@mail.ru
ORCID iD: 0000-0003-1180-2343
SPIN-code: 9211-6391

Cand. Sci. (Biol.)

Russian Federation, 28, Orekhovy blvd, Moscow, 115682; Moscow

Oleg V. Knyazev

Moscow Clinical Scientific Center; State Scientific Centre of Coloproctology

Email: oleg7@bk.ru
ORCID iD: 0000-0001-7250-0977
SPIN-code: 3268-0360

Dr. Sci. (Med.)

Russian Federation, Moscow; Moscow

Vladimir P. Baklaushev

Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies FMBA of Russia

Email: serpoff@gmail.com
ORCID iD: 0000-0003-1039-4245
SPIN-code: 3968-2971

Dr. Sci. (Med.)

Russian Federation, 28, Orekhovy blvd, Moscow, 115682

References

  1. Sairenji T, Collins KL, Evans DV. An update on inflammatory bowel disease. Prim Care. 2017;44(4):673–692. doi: 10.1016/j.pop.2017.07.010
  2. Guindi M, Riddell RH. Indeterminate colitis. J Clin Pathol. 2004;57(12):1233–1244. doi: 10.1136/jcp.2003.015214
  3. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307–317. doi: 10.1038/nature10209
  4. The facts about inflammatory bowel diseases. The Crohn’s & Colitis Foundation of America (CCFA); 2014. Avalable from: https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf
  5. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):17–30. doi: 10.1016/S2468-1253(19)30333-4
  6. Magro F, Portela F. Management of inflammatory bowel disease with infliximab and other anti-tumor necrosis factor alpha therapies. BioDrugs. 2010;24(Suppl 1):3–14. doi: 10.2165/11586290-000000000-00000
  7. Ocansey DK, Qiu W, Wang J, et al. The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer. Stem Cells Int. 2020;2020:7819824. doi: 10.1155/2020/7819824
  8. Tolar J, Le Blanc K, Keating A, et al. Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells. 2010;28(8):1446–1455. doi: 10.1002/stem.459
  9. Williams JT, Southerland SS, Souza J, et al. Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am Surg. 1999; 65:22–26.
  10. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implication for cell-based therapies. Tissue Engl. 2001;7(2):211–228. doi: 10.1089/107632701300062859
  11. Gronthos S, Arthur A, Bartold PM, et al. A method to isolate and culture expand human dental pulp stem cells. J Methods Mol Biol. 2011;698:107–121. doi: 10.1007/978-1-60761-999-4_9
  12. Prockop D. Repair of tissues by adult stem/progenitor cells [MSCs]: controversies, myths, and changing paradigms. Mol Ther. 2009;17(6):939–946. doi: 10.1038/mt.2009.62
  13. Lv FJ, Tuan RS, Cheung KM, et al. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014;32(6):1408–1419. doi: 10.1002/stem.1681
  14. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–15. doi: 10.1016/j.stem.2011.06.008
  15. Wang S, Miao Z, Yang Q, et al. The dynamic roles of mesenchymal stem cells in colon cancer. Can J Gastroenterol Hepatol. 2018;2018:7628763. doi: 10.1155/2018/7628763
  16. Caplan AI. MSCs: The sentinel and safe-guards of injury. J Cell Physiol. 2016;231(7):1413–1416. doi: 10.1002/jcp.25255
  17. Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013;13(4):392–402. doi: 10.1016/j.stem.2013.09.006
  18. Spaggiari GM, Capobianco A, Abdelrazik HF, et al. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2, 3-dioxygenase and prostaglandin E2. Blood. 2008;111(3):1327–1333. doi: 10.1182/blood-2007-02-074997
  19. Terai S, Tsuchiya A. Status of and candidates for cell therapy in liver cirrhosis: overcoming the “point of no return” in advanced liver cirrhosis. J Gastroenterol. 2017;52(2):129–140. doi: 10.1007/s00535-016-1258-1
  20. Yabana T, Arimura Y, Tanaka H, et al. Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity. J Pathol. 2009;218:350–359. doi: 10.1002/path.2535
  21. Dias CB, Milanski M, Portovedo M, et al. Defective apoptosis in intestinal and mesenteric adipose tissue of Crohn’s disease patients. PLoS One. 2014;9(6):e98547. doi: 10.1371/journal.pone.0098547
  22. Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem cell-induced immunoregulation involves FAS-ligand-/FASmediated T cell apoptosis. Cell Stem Cell. 2012;10(5):544–555. doi: 10.1016/j.stem.2012.03.007
  23. Sisakhtnezhad S, Alimoradi E, Akrami H. External factors influencing mesenchymal stem cell fate in vitro. Eur J Cell Biol. 2017;96(1):13–33. doi: 10.1016/j.ejcb.2016.11.003
  24. Chen Q, Yan L, Wang CZ, et al. Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses. World J Gastroenterol. 2013;19(29):4702–4717. doi: 10.3748/wjg.v19.i29.4702
  25. Hidalgo-Garcia L, Galvez J, Rodriguez-Cabezas ME, Anderson PO. Can a conversation between mesenchymal stromal cells and macrophages solve the crisis in the inflamed intestine? Front Pharmacol. 20186;9:179. doi: 10.3389/fphar.2018.00179
  26. Jo H, Eom YW, Kim HS, et al. Regulatory dendritic cells induced by mesenchymal stem cells ameliorate dextran sodium sulfate-induced chronic colitis in mice. Gut Liver. 2018;12(6):664–673. doi: 10.5009/gnl18072
  27. Liu J, Liu Q, Chen X. The immunomodulatory effects of mesenchymal stem cells on regulatory B cells. Front Immunol. 2020;11:1843. doi: 10.3389/fimmu.2020.01843
  28. Самойлова Е.М., Кальсин В.А., Беспалова В.А., и др. Экзосомы — от биологии к клинике // Гены и клетки. 2017. Т. 12, № 4. С. 7–19. [Samoilova EM, Kalsin VA, Bespalova VA, et al. Exosomes — from biology to the clinic. Genes & Cells. 2017;12(4):7–19. (In Russ).] doi: 10.23868/201707024
  29. Zhao T, Sun F, Liu J, et al. Emerging role of mesenchymal stem cell-derived exosomes in regenerative medicine. Curr Stem Cell Res Ther. 2019;14(6):482–494. doi: 10.2174/1574888X14666190228103230
  30. Mianehsaz E, Mirzaei HR, Mahjoubin-Tehran M, et al. Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis? Stem Cell Res Ther. 2019;10(1):340. doi: 10.1186/s13287-019-1445-0
  31. Mendt M, Rezvani K, Shpall E. Mesenchymal stem cell-derived exosomes for clinical use. Bone Marrow Transplant. 2019;54(Suppl 2):789–792. doi: 10.1038/s41409-019-0616-z
  32. Mao F, Yunbing Wu, Xudong Tang, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice. Biomed Res Int. 2017;2017:5356760. doi: 10.1155/2017/5356760
  33. 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 Dis. 2020;11(7):603. doi: 10.1038/s41419-020-02788-0
  34. Ko JZ, Johnson S, Dave M. Efficacy and safety of mesenchymal stem/stromal cell therapy for inflammatory bowel diseases: an up-to-date systematic review. Biomolecules. 2021;11(1):82. doi: 10.3390/biom11010082
  35. Panés J, García-Olmo D, Van Assche G, et al; ADMIRE CD Study Group Collaborators. 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
  36. Herreros MD, Garcia-Olmo D, Guadalajara HT, et al. Stem cell therapy: a compassionate use program in perianal fistula. Stem Cells Int. 2019;2019:6132340. doi: 10.1155/2019/6132340
  37. Garcia-Olmo D, Garcia-Arranz M, Herreros D, et al. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48(7):1416–1423. doi: 10.1007/s10350-005-0052-6
  38. McNevin MS, Lee PY, Bax TW. Martius flap: an adjunct for repair of complex, low rectovaginal fistula. Am J Surg. 2007;193(5):597–599. doi: 10.1016/j.amjsurg.2007.01.009
  39. Cho YB, Park KJ, Yoon SN, et al. Long-Term results of adipose-derived stem cell therapy for the treatment of Crohn’s fistula: ASCs for the treatment of Crohn’s fistula. Stem Cells Transl Med. 2015;4(5):532–537. doi: 10.5966/sctm.2014-0199
  40. Scott LJ. Darvadstrocel: a review in treatment-refractory complex perianal fistulas in Crohn’s disease. BioDrugs. 2018;32(6):627–634. doi: 10.1007/s40259-018-0311-4
  41. Cao Y, Su Q, Zhang B, et al. Efficacy of stem cells therapy for Crohn’s fistula: a meta-analysis and systematic review. Stem Cell Res Ther. 2021;12(1):32. doi: 10.1186/s13287-020-02095-7
  42. Hu J, Zhao G, Zhang L, et al. Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis. Exp Ther Med. 2016;12(5):2983–2989. doi: 10.3892/etm.2016.3724
  43. Zhang J, Lv S, Liu X, et al. Umbilical cord mesenchymal stem cell treatment for Crohn’s disease: a randomized controlled clinical trial. Gut and Liver. 201812(1):73–78. doi: 10.5009/gnl17035
  44. Князев О.В., Парфенов А.И., Коноплянников А.Г., Болдырева О.Н. Использование мезенхимальных стромальных клеток в комплексной терапии язвенного колита // Терапевтический архив. 2016. Т. 88, № 2. C. 44–48. [Knyazev OV, Parfenov AI, Konoplyannikov AG, Boldyreva ON. The use of mesenchymal stromal cells in the complex therapy of ulcerative colitis. Therapeutic archive. 2016;88(2):44–48. (In Russ).]
  45. Князев О.В., Каграманова А.В., Фадеева Н.А., и др. Мезенхимальные стромальные клетки костного мозга и азатиоприн в терапии болезни Крона // Терапевтический архив. 2018. Т. 90. № 2. C. 47–52. [Knyazev OV, Kagramanova AV, Fadeeva NA, et al. Bone marrow mesenchymal stromal cells and azathioprine in the treatment of Crohn’s disease. Therapeutic archive. 2018;90(2):47–52. (In Russ).] doi: 10.26442/terarkh201890247-52
  46. Князев О.В., Фадеева Н.А., Каграманова А.В., и др. Клеточная терапия перианальных проявлений болезни Крона // Терапевтический архив. 2018. Т. 90, № 3. C. 60–66. [Knyazev OV, Fadeeva NA, Kagramanova AV, et al. Cell therapy of the perianal manifestations of Crohn’s disease. Therapeutic archive. 2018;90(3):60–66. (In Russ).] doi: 10.26442/terarkh201890360-66

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. General MSC’s effects grouped by the two fundamental mechanisms: 1) direct cell differentiation of recruited MSC (into cells of adipose, bone, cartilage and muscle tissues) to replace damaged cells and 2) induction of cytokines secreted by MSC into the inflammatory medium, affecting the recipient’s immune system (IL-6: interleukin-6; PGE2: prostaglandin E2; TGF-β: β-transforming growth factor; IDO: indoleamine-2,3-dioxygenase; CCL-2: С-С-chemokine ligand 2; IL-10: interleukin -10; HGF: hepatocyte growth factor; MMP: matrix metalloproteinases; HLA-G: human leukocyte antigen-G). Adapted from [7].

Download (293KB)
Indexing metadata

Copyright (c) 2021 Konoplyannikov M.A., Knyazev O.V., Baklaushev V.P.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies