Mesenchymal Stem Cells for the Treatment of Acetic Acid-Induced Ulcerative Colitis in Rats


  • Thoria Ahmed Omar Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
  • Eman Sweed Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
  • Dina Sweed Department of Pathology, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
  • Rawhia Hassan Eledel Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
  • Dalia Hosny Abou-Elela Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
  • Gehad Hikal Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt



Inflammatory bowel diseases, Ulcerative colitis, Acetic acid, Mesenchymal stem cells, Immunomodulatory, Anti-inflammatory


Background: Ulcerative colitis (UC) is an autoimmune inflammatory bowel disease, characterized by chronic and relapsing inflammation of the intestinal mucosa. Clinical treatments fail to reduce inflammation and induce side effects in nearly 30% of patients. Mesenchymal stem cells (MSCs) are immunomodulatory agents that can encourage tissue repair and regeneration.

Aim: To investigate the ability of MSCs to differentiate into enterocytes under the mediation of activin a, fibroblastic growth factor 2, and epidermal growth factors and to study the effect of administering MSCs to rats with acetic acid (AA)-induced UC.

Methods: MSCs isolated from the umbilical cord were induced to differentiate into enterocytes. The induced cells were morphologically evaluated by flow cytometry and immunocytochemistry. Forty rats were divided into four groups: control, AA-induced UC, differentiated, and undifferentiated MSC treated groups. The acute UC in rats was induced by 3% AA transrectal administration. Body weight changes, disease activity index (DAI), and histopathological and immunohistochemical CD105 and CD34 staining were recorded. IL-17, IL-10, and TGF- β levels were measured as well.

Results: In Both differentiated and undifferentiated MSCs, induced MSCs improved the DAI score and significantly recovered the pathological changes. The favorable effect of MSCs was significantly linked to CD105 overexpression and CD34 low expression. IL-10 and TGF-β levels increased while IL-17 levels decreased.

Conclusion: Both differentiated and undifferentiated MSCs showed anti-inflammatory and immunomodulatory effects in our study. Based on our results, MSCs could become potentially useful for regenerative medicine and the clinical treatment of UC.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Moein S, Vaghari-Tabari M, Qujeq D, Majidinia M, Nabavi SM, Yousefi B. MiRNAs and inflammatory bowel disease: An interesting new story. J Cell Physiol. 2019;234(4):3277-93. PMid:30417350 DOI:

Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448(7152):427-34. PMid:17653185 DOI:

Terry R, Chintanaboina J, Patel D, Lippert B, Haner M, Price K, et al. Expression of WIF-1 in inflammatory bowel disease. Histol Histopathol. 2019;34(2):149-57. PMid:30051904

Neurath MF. Current and emerging therapeutic targets for IBD. Nat Rev Gastroenterol Hepatol. 2017;14(5):269-78. PMid:28144028 DOI:

Safarpour AR, Hosseini SV, Mehrabani D. Epidemiology of inflammatory bowel diseases in iran and Asia; a mini review. Iran J Med Sci. 2013;38(Suppl 2):140-9 PMid:24031103

Mehrabani D, Khajehahmadi Z, Tajik P, Tamadon A, Rahmanifar F, Ashraf M, et al. Regenerative effect of bone marrow-derived mesenchymal stem cells in thioacetamide-induced liver fibrosis of rats. Arch Razi Inst. 2019;74(3):279-86.

Mehrabani D, Mehrabani G, Zare S, Manafi A. Adipose-derived stem cells (ADSC) and aesthetic surgery: A mini review. World J Plast Surg. 2013;2(2):65-70. PMid:25489507

Iwao T, Toyota M, Miyagawa Y, Okita H, Kiyokawa N, Akutsu H, et al. Differentiation of human induced pluripotent stem cells into functional enterocyte-like cells using a simple method. Drug Metab Pharmacokinet. 2014;29(1):44-51. PMid:23822979 DOI:

Ogaki S, Shiraki N, Kume K, Kume S. Wnt and Notch signals guide embryonic stem cell differentiation into the intestinal lineages. Stem Cells. 2013;31(6):1086-96. PMid:23378042 DOI:

El-Akabawy G, El-Sherif NM. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomed Pharmacother. 2019;111:841-51. PMid:30616083 DOI:

Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother. 2013;4(4):303-6. PMid:24250214 DOI:

Soontararak S, Chow L, Johnson V, Coy J, Wheat W, Regan D, 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 Transl Med. 2018;7(6):456-67. PMid:29635868 DOI:

Lopez-Santalla M, Hervas-Salcedo R, Fernandez-Garcia M, Bueren JA, Garin MI. Cell therapy with mesenchymal stem cells induces an innate immune memory response that attenuates experimental colitis in the long term. J Crohns Colitis. 2020;14(10):1424-35. PMid:32318720 DOI:

Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Des Devel Ther. 2015;9:3923-34. PMid:26251571 DOI:

Helal OK, Metwaly HG, Abo Gazia MM, El Desoki R, El Ashmouny N. The possible therapeutic effect of mesenchymal stem cells and Vitamin E on experimentally induced ulcerative colitis in adult male albino rats: Histological and immunohistochemical study. Benha Med J. 2021;38(1):294-321. DOI:

Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Löfberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47(3):404-9. PMid:10940279 DOI:

Araki Y, Mukaisyo K, Sugihara H, Fujiyama Y, Hattori T. Increased apoptosis and decreased proliferation of colonic epithelium in dextran sulfate sodium-induced colitis in mice. Oncol Rep. 2010;24(4):869-74. PMid:20811666 DOI:

Tampakis A, Weixler B, Rast S, Tampaki EC, Cremonesi E, Kancherla V, et al. Nestin and CD34 expression in colorectal cancer predicts improved overall survival. Acta Oncol. 2021;60(6):727-34. PMid:33734917 DOI:

Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018;53(3):305-53. PMid:29429045 DOI:

Nakahashi-Oda C, Udayanga KG, Nakamura Y, Nakazawa Y, Totsuka N, Miki H, et al. Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces. Nat Immunol. 2016;17(4):441-50. PMid:26855029 DOI:

He XW, He XS, Lian L, Wu XJ, Lan P. Systemic infusion of bone marrow-derived mesenchymal stem cells for treatment of experimental colitis in mice. Dig Dis Sci. 2012;57(12):3136-44. PMid:22752635 DOI:

Song WJ, Li Q, Ryu MO, Ahn JO, Bhang DH, Jung YC, et al. TSG-6 released from intraperitoneally injected canine adipose tissue-derived mesenchymal stem cells ameliorate inflammatory bowel disease by inducing M2 macrophage switch in mice. Stem Cell Res Ther. 2018;9(1):91. PMid:29625582 DOI:

Lin Y, Lin L, Wang Q, Jin Y, Zhang Y, Cao Y, et al. Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium-induced colitis in mice. Clin Exp Pharmacol Physiol. 2015;42(1):76-86. PMid:25311720 DOI:

Shi G, Wang G, Lu S, Li X, Zhang B, Xu X, et al. PD-L1 is required for human endometrial regenerative cells-associated attenuation of experimental colitis in mice. Am J Transl Res. 2019;11(8):4696-712. PMid:31497192

Zhang D, Zheng L, Shi H, Chen X, Wan Y, Zhang H, et al. Suppression of peritoneal tumorigenesis by placenta-derived mesenchymal stem cells expressing endostatin on colorectal cancer. Int J Med Sci. 2014;11(9):870-9. PMid:25013366 DOI:

Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5⁺ stem cell. Nat Med. 2012;18(4):618-23. PMid:22406745 DOI:

Miyamoto S, Ohnishi S, Onishi R, Tsuchiya I, Hosono H, Katsurada T, et al. Therapeutic effects of human amnion-derived mesenchymal stem cell transplantation and conditioned medium enema in rats with trinitrobenzene sulfonic acid-induced colitis. Am J Transl Res. 2017;9(3):940-52. PMid:28386323

Legaki E, Roubelakis MG, Theodoropoulos GE, Lazaris A, Kollia A, Karamanolis G, et al. Therapeutic potential of secreted molecules derived from human amniotic fluid mesenchymal stem/stroma cells in a mice model of colitis. Stem Cell Rev Rep. 2016;12(5):604-12. PMid:27503204 DOI:

Lee KE, Jung SA, Joo YH, Song EM, Moon CM, Kim SE, et al. The efficacy of conditioned medium released by tonsil-derived mesenchymal stem cells in a chronic murine colitis model. PLoS One. 2019;14(12):e0225739. PMid:31790467 DOI:

Wang M, Liang C, Hu H, Zhou L, Xu B, Wang X, et al. Intraperitoneal injection (IP), Intravenous injection (IV) or anal injection (AI)? Best way for mesenchymal stem cells transplantation for colitis. Sci Rep. 2016;6:30696. PMid:27488951 DOI:

Hoshino A, Hashimoto H, Arihiro S, Hori M, Tajiri H, Kusakabe M. Su1896 Tenascin-C mediates the suppressive effects on inflammation by the mesenchymal stem cell in dextran sulfate sodium induced colitis. Gastroenterology. 2015;148(4):S-547. DOI:

Borzou B, Mehrabani D, Zare S, Zamani-Pereshkaft M, Acker JP. The effect of age and type of media on growth kinetics of human amniotic fluid stem cells. Biopreserv Biobank. 2020;18(5):389-94. PMid:32799559 DOI:

Al Naem M, Bourebaba L, Kucharczyk K, Röcken M, Marycz K. Therapeutic mesenchymal stromal stem cells: Isolation, characterization and role in equine regenerative medicine and metabolic disorders. Stem Cell Rev Rep. 2020;16(2):301-22. PMid:31797146 DOI:

Yu F, Lu Z, Huang K, Wang X, Xu Z, Chen B, et al. MicroRNA- 17-5p-activated Wnt/β-catenin pathway contributes to the progression of liver fibrosis. Oncotarget. 2016;7(1):81-93. PMid:26637809 DOI:

Qiu S, Kabeya T, Ogawa I, Anno S, Hayashi H, Kanaki T, et al. Gellan gum promotes the differentiation of enterocytes from human induced pluripotent stem cells. Pharmaceutics. 2020;12(10):951. PMid:33050367 DOI:

Li S, Huang Q, Mao J, Li Q. FGF signaling mediates definitive endoderm formation by regulating epithelial-to-mesenchymal transition and cell proliferation. Int J Dev Biol. 2020;64(10-11- 12):471-7. PMid:33336709 DOI:

Ye L, Sun LX, Wu MH, Wang J, Ding X, Shi H, et al. A Simple system for differentiation of functional intestinal stem cell-like cells from bone marrow mesenchymal stem cells. Mol Ther Nucleic Acids. 2018;13:110-20. PMid:30268688 DOI:

Wang Y, Liu XP, Zhao ZB, Chen JH, Yu CG. Expression of CD4+ forkhead box P3 (FOXP3)+ regulatory T cells in inflammatory bowel disease. J Dig Dis. 2011;12(4):286-94. PMid:21791023 DOI:

Kim HS, Shin TH, Lee BC, Yu KR, Seo Y, Lee S, et al. Human umbilical cord blood mesenchymal stem cells reduce colitis in mice by activating NOD2 signaling to COX2. Gastroenterology. 2013;145(6):1392-403. e8. PMid:23973922 DOI:




How to Cite

Omar TA, Sweed E, Sweed D, Eledel RH, Abou-Elela DH, Hikal G. Mesenchymal Stem Cells for the Treatment of Acetic Acid-Induced Ulcerative Colitis in Rats. Open Access Maced J Med Sci [Internet]. 2022 Aug. 27 [cited 2023 Mar. 31];10(A):1478-86. Available from: