Therapeutic efficiency of adipose-derived mesenchymal stem cells in healing of experimentally induced gastric ulcers in rats

다국어 초록 (Multilingual Abstract)

Gastric (peptic) ulcer is a major gastrointestinal disorder with high morbidity and mortality. While several drugs have been used to treat gastric ulcers, such as proton pump inhibitor-based triple therapy for Helicobacter pylori eradication, but hey result in adverse side effects. Therefore, development of new alternative therapies is desirable. Many recent studies have shown that mesenchymal stem cells (MSCs) might have an enhancing effect on the ulcerated gastric mucosa. The aim of this study is to evaluate the efficacy of MSCs in the treatment of indomethacin-induced gastric ulcer, and to compare it with the normal ulcer autohealing. This work was performed on 36 adult male albino rats, divided into four groups: Group I (control group), Group II (ulcer group), Group III (autohealing group), and Group IV (stem cells-treated group). The histological changes of gastric mucosa were examined in sections stained with H&E using light microscope for expression of vascular endothelial growth factors (VEGF) and proliferating cell nuclear antigen (PCNA) in immunohistochemical stained sections using image analyzer. The results from MSCs-treated group revealed restoration of the normal architecture of the gastric mucosa with comparison to the autohealing group which showed excessive granulation tissue and heavy cellular infiltration with disorganized architecture of the fundic mucosa. Immunohistochemical examination showed strong expression of both VEGF and PCNA in the MSCs-treated group. So it was concluded that MSCs accelerate gastric ulcer healing when injected intraperitoneally, compared to autohealing process which showed delayed healing.

목차 (Table of Contents)

• Introduction Materials and Methods Results Discussion ORCID Author Contributions Conflicts of Interest Acknowledgements References

참고문헌 (Reference)

1 Connolly DT, "Vascular permeability factor: a unique regulator of blood vessel function" 47 : 219-223, 1991

2 Liu ZJ, "Trafficking and differentiation of mesenchymal stem cells" 106 : 984-991, 2009

3 Hayashi Y, "Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats" 294 : G778-G786, 2008

4 Choi HS, "Therapeutic potentials of human adipose-derived stem cells on the mouse model of Parkinson’s disease" 36 : 2885-2892, 2015

5 Bancroft JD, "Theory and practice of histological techniques" Churchill Livingstone Elsevier 2008

6 Werther JL, "The gastric mucosal barrier" 67 : 41-53, 2000

7 Meligy FY, "The efficiency of in vitro isolation and myogenic differentiation of MSCs derived from adipose connective tissue, bone marrow, and skeletal muscle tissue" 48 : 203-215, 2012

8 Atuma C, "The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo" 280 : G922-G929, 2001

9 Vanwijck R, "Surgical biology of wound healing" 156 : 175-184, 2001

10 Tuch BE, "Stem cells--a clinical update" 35 : 719-721, 2006

11 Binato R, "Stability of human mesenchymal stem cells during in vitro culture:considerations for cell therapy" 46 : 10-22, 2013

12 Khazaei M, "Protective effect of falcaria vulgaris extract on ethanol induced gastric ulcer in rat" 5 : 43-46, 2006

13 Fan H, "Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis" 9 : 473-481, 2012

14 Jiang H, "Potential role of mesenchymal stem cells in alleviating intestinal ischemia/reperfusion impairment" 8 : e74468-, 2013

15 Najm WI, "Peptic ulcer disease" 38 : 383-394, 2011

16 Abraham NS, "National adherence to evidencebased guidelines for the prescription of nonsteroidal antiinflammatory drugs" 129 : 1171-1178, 2005

17 Wallace JL, "NSAIDinduced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2" 119 : 706-714, 2000

18 Danese S, "Mesenchymal stromal cells in inflammatory bowel disease: conspirators within the ‘colitogenic niche’?" 62 : 1098-1099, 2013

19 Teixeira FG, "Mesenchymal stem cells secretome:current trends and future challenges" 15 : 75-77, 2020

20 Sibov TT, "Mesenchymal stem cells from umbilical cord blood:parameters for isolation, characterization and adipogenic differentiation" 64 : 511-521, 2012

21 Devine SM, "Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion" 29 : 244-255, 2001

22 Ren G, "Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide" 2 : 141-150, 2008

23 Satija NK, "Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine" 13 : 4385-4402, 2009

24 Jo YY, "Isolation and characterization of postnatal stem cells from human dental tissues" 13 : 767-773, 2007

25 Francis MP, "Isolating adiposederived mesenchymal stem cells from lipoaspirate blood and saline fraction" 6 : 11-14, 2010

26 Jones MK, "Inhibition of angiogenesis by nonsteroidal antiinflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing" 5 : 1418-1423, 1999

27 El-Mehi AE, "Influence of acrylamide on the gastric mucosa of adult albino rats and the possible protective role of rosemary" 47 : 273-283, 2015

28 Chang Q, "In vivo transplantation of bone marrow mesenchymal stem cells accelerates repair of injured gastric mucosa in rats" 125 : 1169-1174, 2012

29 Thomson AW, "Immunoregulatory functions of mTOR inhibition" 9 : 324-337, 2009

30 Nauta AJ, "Immunomodulatory properties of mesenchymal stromal cells" 110 : 3499-3506, 2007

31 Toma C, "Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart" 105 : 93-98, 2002

32 Bernardo ME, "Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms" 67 : 9142-9149, 2007

33 Kallmeyer K, "Homing properties of mesenchymal stromal cells" 15 : 477-479, 2015

34 Bai L, "Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models" 15 : 862-870, 2012

35 Matsumoto K, "Hepatocyte growth factor (HGF)as a tissue organizer for organogenesis and regeneration" 239 : 639-644, 1997

36 Razban V, "HIF-1α overexpression induces angiogenesis in mesenchymal stem cells" 1 : 174-183, 2012

37 Sonnenberg A, "Geographic and temporal variations in the occurrence of peptic ulcer disease" 110 : 11-24, 1985

38 Inas Z, "Gastroprotective effect of Cordia myxa L. fruit extract against indomethacin-induced gastric ulceration in rats" 8 : 433-445, 2011

39 Lichtenberger LM, "Gastroduodenal mucosal defense" 15 : 463-472, 1999

40 Ham M, "Gastroduodenal defense" 23 : 607-616, 2007

41 Modlin IM, "Gastric stem cells: an update" 52 : 134-137, 2003

42 Yang H, "Expression pattern, regulation, and functions of methionine adenosyltransferase 2beta splicing variants in hepatoma cells" 134 : 281-291, 2008

43 Abd-Elmenm S, "Evaluation of the role of adipose-derived stem cells in the healing of indomethacin-induced gastric ulceration in rats" 7 : 246-, 2016

44 Baatar D, "Esophageal ulceration activates keratinocyte growth factor and its receptor in rats: implications for ulcer healing" 122 : 458-468, 2002

45 Abbas AM, "Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats" 69 : 527-537, 2013

46 Chaturvedi A, "Effect of ethanolic extract of Eugenia jambolana seeds on gastric ulceration and secretion in rats" 51 : 131-140, 2007

47 Kunchandy J, "Effect of alpha2 agonists clonidine, guanfacine and B-HT 920 on gastric acid secretion and ulcers in rats" 275 : 123-138, 1985

48 Ali S, "Effect of Musa sapientum (Banana) on indomethacin-induced gastric mucosal injury in rats: histological study" 2 : 11-28, 2018

49 Al-sagaaf S, "Does commercial aloe vera protects the structure of the gastric mucosa against acute nonsteroidal anti-inflammatory drug (diclofenac sodium)-induced damage?" 34 : 80-91, 2011

50 Fakhry J, "Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine" 369 : 245-253, 2017

51 Suleyman H, "Different mechanisms in formation and prevention of indomethacininduced gastric ulcers" 33 : 224-234, 2010

52 Thong-Ngam D, "Curcumin prevents indomethacin-induced gastropathy in rats" 18 : 1479-1484, 2012

53 Chatzaki E, "Corticotropinreleasing factor (CRF) receptor type 2 in the human stomach:protective biological role by inhibition of apoptosis" 209 : 905-911, 2006

54 Takahashi H, "Comparison of proliferating cell nuclear antigen expression in odontogenic keratocyst and ameloblastoma: an immunohistochemical study" 16 : 185-192, 1998

55 Zickri MB, "Comparative study between intravenous and intraperitoneal stem cell therapy in amiodarone induced lung injury in rat" 7 : 1-11, 2014

56 Rafei M, "Allogeneic mesenchymal stem cells for treatment of experimental autoimmune encephalomyelitis" 17 : 1799-1803, 2009

57 Ezquer F, "Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy" 8 : 20-, 2017

58 González MA, "Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses" 136 : 978-989, 2009

59 Badhani S, "A review on some Indian medicinal plants for antiulcer activity" 1 : 6-9, 2012

60 Seifried HE, "A review of the interaction among dietary antioxidants and reactive oxygen species" 18 : 567-579, 2007