Skip to main content

Advertisement

SpringerLink
Log in

Mesenchymal stem cells improve the healing of ischemic colonic anastomoses (experimental study)

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Objective

The goal of this study is to examine if allogenic mesenchymal stem cell (MSC) transplantation is a useful therapy for left ischemic colon anastomosis in rats.

Summary and background data

Problems with anastomosis healing may lead to serious postoperative complications. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are also referred to as stromal progenitor cells, are self-renewing and expandable stem cells. Recent studies have suggested that BM-MSCs play a crucial role in the processes of intestinal repair and accelerate angiogenesis.

Methods

MSCs were isolated from rats before analysis by light and scanning electron microscopy. Forty male Wistar albino rats weighing 250–280 g were divided into four equal groups (n = 10) as follows: group 1: control, ischemic left colonic anastomoses (fourth day); group 2: control, ischemic left colonic anastomoses (seventh day); group 3: ischemic left colonic anastomoses + locally transplanted BM-MSCs (fourth day); group 4: ischemic left colonic anastomoses + locally transplanted BM-MSCs (seventh day). Histopathological features and anastomotic strength were evaluated.

Results

BM-MSCs therapy significantly accelerated all of the healing parameters for ischemic colonic anastomosis except for inflammation on the fourth day. On the seventh day, BM-MSCs augmented the levels of the hydroxyproline and bursting pressure. Histological parameters, especially angiogenesis, were also found to be important for healing of ischemic colonic anastomoses.

Conclusions

This is the first study to use locally transplanted cell therapy for the healing of ischemic colonic anastomosis. BM-MSCs therapy significantly accelerated all of the healing parameters for ischemic colonic anastomosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Guven A, Pehlivan M, Gokpinar I, Gurleyik E, Cam M (2007) Early glutamine-enriched enteral feeding facilitates colonic anastomosis healing: light microscopic and immunohistochemical evaluation. Acta Histochem 109:122–129

    Article  CAS  PubMed  Google Scholar 

  2. Verhofstad HJM, Lange PW, van der Laak J, Verhofstad AJ, Hendriks T (2002) Microscopic analysis of anastomotic healing in the intestine of normal and diabetic rats. Dis Colon Rectum 44:423–431

    Article  Google Scholar 

  3. Egger B, Inglin R, Zeek J, Dirsch O, Huang Y, Büchler MW (2001) Insulin like growth factor I and truncated keratinocyte growth factor accelerate healing of left sided colonic anastomoses. Br J Surg 88:90–98

    Article  CAS  PubMed  Google Scholar 

  4. Hamzaoglu I, Karahasanoglu T, Aydın S, Sahin AD, Carkman S, Sarıyar M, Alemdaroglu K (1998) The effects of hyperbaric oxygen on normal and ischemic colon anastomoses. Am J Surg 176:458–461

    Article  CAS  PubMed  Google Scholar 

  5. Garcia JG, Criado CG (1998) Healing of colonic ischemic anastomoses in the rats. Dis Colon Rectum 41:829–895

    Article  Google Scholar 

  6. Pascual I, Miguel FG, Pinedeo-Gomez UA, Arranz GM, Olmo-Garcia D (2008) Adipose-derived mesenchymal stem cells in biosutures do not improve healing of experimental colonic anastomoses. Br J Surg 95:1180–1184

    Article  CAS  PubMed  Google Scholar 

  7. Gao F, He Tao, Wang H, Yu S, Yi D, Liu W, Cai Z (2007) A promising strategy for the treatment of ischemic heart disease: mesenchymal stem cell-mediated vascular endothelial growth factor gene transfer in rats. Can J Cardiol 23:891–898

    PubMed  Google Scholar 

  8. Wu Y, Chen L, Scott GP, Tredget E (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25:2648–2659

    Article  CAS  PubMed  Google Scholar 

  9. Day MR (2006) Epithelial stem cells and tissue engineered intestine. Curr Stem Cell Res Ther 1:1113–1120

    Article  Google Scholar 

  10. Piao H, Youn TJ, Kwon JS (2005) Effects of bone marrow derived mesenchymal stem cells transplantation in acutely infarcting myocardium. Eur J Heart Fail 7:730–738

    Article  CAS  PubMed  Google Scholar 

  11. Hayashi Y, Tsuji S, Tsuji M, Nishida T, Ishii S, Lijima H, Nakamura T, Eguchi H, Miyoshi E, Hayashi N, Kawano S (2008) Topical implantation of mesenchymal stem cells has beneficial effects on healing of experimental colitis in rats. J Pharmacol Exp Ther 326:523–531

    Article  CAS  PubMed  Google Scholar 

  12. Karaoz E, Aksoy A, Ayhan S, Sariboyacı AE, Kaymaz F, Kasap M (2009) Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol 132:533–546

    Article  CAS  PubMed  Google Scholar 

  13. Andoh A, Bamba S, Fujiyama Y, Brittan M, Wright AN (2005) Colonic subepithelial myofibroblast in mucosal inflammation and repair: contribution of bone marrow-derived stem cells to the gut regenerative response. J Gastroenterol 40:1089–1099

    Article  PubMed  Google Scholar 

  14. Tadauchi A, Narita Y, Kagami H, Niwa Y, Ueda M, Goto H (2009) Novel cell-based therapeutic strategy for ischemic colitis with use of bone marrow-derived mononuclear cells in rats. Dis Colon Rectum 52:1443–1451

    PubMed  Google Scholar 

  15. Donzelli E, Salvade A, Mimo P, Vigano M, Morrone M, Papagna R, Carini F, Zaopo A, Miloso M, Baldoni M, Tredici G (2007) Mesenchymal stem cells cultured on collagen scaffold: in vitro osteogenic differentiation. Arch Oral Biol 52:64–73

    Article  CAS  PubMed  Google Scholar 

  16. Yu Y, Yao AH, Chen N, Pu LY, Fan Y, Lv L, Sun BC, Li GQ, Wang XH (2007) Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration. Mol Ther 15:1382–1389

    Article  CAS  PubMed  Google Scholar 

  17. Braga LM, Lacchini S, Schaan BD, Rodriques B, Rosa K, Angelis K, Borges LF, Iriqoyen MC, Nardi NB (2008) In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction. J Biomed Sci 3:365–374

    Article  Google Scholar 

  18. Hammarlund C (1999) The physiologic effects of hyperbaric oxygenation. In: Kindwall EP, Whelan HT (eds) Hyperbaric medicine practice, 2nd edn. Best, Flagstaff, pp 37–65

  19. Friedman HF, Fitzmaurice M, Lefaivre JF, Vecchiolla TS, Clarke D (2006) An evidence-based appraisal of the use of hyperbaric oxygen on flaps and grafts. Plast Reconstr Surg 117:175–190

    Article  Google Scholar 

  20. Machine A, Rohr S, Toti F (1999) Wound healing with hyperbaric oxygen: experimental study of the angiogenesis phase in the rat. Ann Chir 53:307–311

    Google Scholar 

  21. Gupta A, Dixit A, Sales MK, Winslet CM, Seifalian MA (2006) Tissue engineering of small intestine—current status. Biomacromolecules 7:2701–2709

    Article  CAS  PubMed  Google Scholar 

  22. Weil RB, Markel AT, Hermann LJ, Abarbanell A, Meldrum RD (2009) Mesenchymal stem cells enhance the viability and proliferation of human fetal intestinal epithelial cells following hypoxic injury via paracrine mechanisms. Surgery 146:190–197

    Article  PubMed  Google Scholar 

  23. Christensen H, Oxlund H (1994) Growth hormone increases the collagen deposition rate and breaking strength of left colonic anastomoses in rats. Surgery 116:550–556

    CAS  PubMed  Google Scholar 

  24. Mast BA (1997) Healing in other tissues. Surg Clin North Am 77:529–547

    Article  CAS  PubMed  Google Scholar 

  25. Oxlund H, Christensen H, Seyer-Hansen M, Andreasses TT (1996) Collagen deposition and mechanical strength of colon anastomoses and skin incisional wounds of rats. J Surg Res 66:25–30

    Article  CAS  PubMed  Google Scholar 

  26. Dubay AD, Franz MG (2003) Acute wound healing: the biology of acute wound failure. Surg Clin N Am 83:463–481

    Article  PubMed  Google Scholar 

  27. Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C, Kearney M, Chen D, Symes JF, Fishman MC, Huang PL, Isner JM (1998) Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 101:2567–2578

    Article  CAS  PubMed  Google Scholar 

  28. Makela J, Ylitalo K, Lehtonen S et al (2007) Bone marrow-derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site. J Thorac Cardiovasc Surg 134:565–657

    Article  PubMed  Google Scholar 

  29. Phinney GD, Prockop JD (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and models of tissue repair—current views. Stem Cells 25:2896–2902

    Article  PubMed  Google Scholar 

  30. Brittan M, Chance V, Elia G, Poulsom R, Alison MR, MacDonald TT, Wright NA (2005) A regenerative role for bone marrow following experimental colitis: contribution to neovasculogenesis and myofibroblasts. Gastroenterology 128(7):1984–95

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Surgery, Okmeydani Education and Research Hospital, Istanbul, Turkey

    Gokhan Adas, Oguzhan Karatepe & Ozgur Kemik

  2. Department of Surgery, Istanbul Education and Research Hospital, Istanbul, Turkey

    Soykan Arikan

  3. Stem Cell and Gene Therapy Research and Applied Center, Kocaeli University, Kocaeli, Turkey

    Selda Ayhan & Erdal Karaoz

  4. Department of Pathology, Okmeydani Education and Research Hospital, Istanbul, Turkey

    Gulcin Kamali

  5. Department of Immunology, Istanbul Faculty of Medicine, Istanbul, Turkey

    Bahar Eryasar

  6. Department of Genetics, Institute for Experimental Medicine, Istanbul Faculty of Medicine, Istanbul, Turkey

    Duran Ustek

  7. Department of Surgery Sisli/Okmeydani, Okmeydani Training Hospital, 34715, Istanbul, Turkey

    Oguzhan Karatepe

Authors
  1. Gokhan Adas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soykan Arikan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oguzhan Karatepe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ozgur Kemik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Selda Ayhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Erdal Karaoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gulcin Kamali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bahar Eryasar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Duran Ustek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oguzhan Karatepe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adas, G., Arikan, S., Karatepe, O. et al. Mesenchymal stem cells improve the healing of ischemic colonic anastomoses (experimental study). Langenbecks Arch Surg 396, 115–126 (2011). https://doi.org/10.1007/s00423-010-0717-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-010-0717-z

Keywords

Search

Navigation