The Effects of Adipose-Derived Stem Cells (ADSC) Autograft in the Viability of Random Skin Flap in Rats

Shobeyri, H; Akbari, H; Fatemi, MJ; Saberi, M

The Effects of Adipose-Derived Stem Cells (ADSC) Autograft in the Viability of Random Skin Flap in Rats

Document Type : Original Article

Authors

H Shobeyri ¹

H Akbari ²

MJ Fatemi ³

M Saberi ⁴

¹ Assistant Professor, Department of Reconstructive and Plastic Surgery, Iran University of Medical Sciences, Hazrat Fatemeh Hospital

² Assistant Professor of Plastic & Reconstructive Surgery, Burn Research Center, Iran University of Medical Sciences, Hazrate Fateme Hospital, Tehran, Iran

³ Professor, Department of Reconstructive and Plastic Surgery, Iran University of Medical Sciences, Hazrat Fatemeh Hospital, Burn Research Center

⁴ Assistant Professor, Department of Social Medicine, Baqiyatullah University of Medical Sciences, Medicine, Quran and Hadith Research Center

Abstract

Introduction & Objective: Flap necrosis caused by inadequate blood flow to a common complication of surgery is reconstructive. Since the angiogenic potential of stem cells has been shown, the purpose of this study was to evaluate the effect of adipose-derived stem cells autograft rate of random skin flap angiogenesis animal model rat. Materials & Methods: This experimental study in 1394 in laboratory animals Hazrat Fatima (SA) was conducted. In this study, 24 male Sprague-Dawley, rats weighing 300-350 g were divided into two groups after anesthesia. In the study group of stem cells from fat tissue autograft were inguinal area and cultured and then injected subcutaneously at the base of random flap in the control group received saline. On days 7 and 14 photographs were taken to determine the extent of necrosis flap and then the flap base for histopathological examination on day fourteen and counting the number of capillaries were sampled. At the end, the data were analyzed by using 19 SPSS software and paired samples t-test. Results: The comparison between the two groups showed areas of flap survival on the seventh day of the stem cell group 10.592 ± 1.095 and in the control group 5.793 ± 2.023 and on the fourteenth day respectively 10.769 ± 0.934 and 5.519 ± 2.107, the difference was significant (P < 0.001). Results angiogenesis stem cell group 27.666 ± 10.201 and control 12.750 ± 6.810 and the difference in the two groups was significant (P < 0.001), so that the average of the group is more stem cells. Conclusions: These findings suggest that adipose-derived stem cells have the potential to improve the survival of random flap. This mechanism can also differentiate these cells into endothelial cells or indirectly by increasing angiogenesis is.

Keywords

Adipose-Derived Stem Cells

Angiogenesis

Random Flap

1. Schmid MH, Meuli-Simmen C, Hafner J. Repair of cutaneous defects after skin cancer surgery. Recent Results Cancer Res2002; 160: 225-233.

2. McGregor IA, Morgan G. Axial and random pattern flaps. Br J Plast Surg1973; 26: 202-213.

3. Lu Feng, Hiroshi Mizuno, Cagri A. Uysal, et al. Improved Viability of Random Pattern Skin Flaps through the Use of Adipose-Derived Stem Cells. Plast. Reconstr. Surg. 2008; 121: 50.

4. Li QF, Reis ED, Zhang WX, Silver L, Fallon JT, Weinberg H. Accelerated flap prefabrication with vascular endothelial growth factor. Journal of reconstructive microsurgery. 2000 Jan; 16(01):
0045-50.

5. Zhang F, Fischer K, Komorowska-Timek E, Guo M, Cui D, Dorsett-Martin W, Buncke HJ, Lineaweaver WC. Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model. Annals of plastic surgery. 2001 Mar 1; 46(3): 314-9.

6. Pang Y, Lineaweaver WC, Lei MP, Oswald T, Shamburger S, Cai Z, Zhang F. Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic flap survival in rats. Plast Reconstr Surg2003; 112: 556-564.

7. Yang M, Sheng L, Li H, Weng R, Li QF. Improvement of the skin flap survival with the bone marrow-derived mononuclear cells transplantation in a rat model. Microsurgery. 2010 May; 30(4): 275-81.

8. Lee DW, Jeon YR, Cho EJ, Kang JH, Lew DH. Optimal administration routes for adipose-derived stem cells therapy in ischaemic flaps. J Tissue Eng Regen Med. 2014 Aug; 8(8): 596-603.

9. Simman R, Craft C, McKinney B. Improved survival of ischemic random skin flaps through the use of bone marrow nonhematopoietic stem cells and angiogenic growth factors. Annals of plastic surgery. 2005 May 1; 54(5): 546-52.

10. Tepper OM, Galiano RD, Kalka C, et al. Endothelial progenitor cells: the promise of vascular stem cells for plastic surgery. Plast Reconstr Surg. 2003; 111: 846.

11. Richards L, Lineaweaver WC, Stile F, et al. Effect of hyperbaric oxygen therapy on the tubed pedicle flap survival in a rat model. Ann Plast Surg 2003; 50: 51-56.

12. Kitlowski EA. A simple method for gradual occlusion of circulation in tubed pedicle flaps. Plast Reconstr Surg1954; 13: 162-166.

13. Karacaoglu E, Yuksel F, Turan SO, et al. Chemical delay: an alternative to surgical delay experimental study. Ann Plast Surg 2002; 49: 73-80.

14. Stark GB, Hong C, Futrell JW. Enhanced neovascularization of rat tubed pedicle flaps with low perfusion of the wound margin. Plast Reconstr Surg1987; 80: 814-824.

15. Park SS, Rodeheaver GT, Levine PA. Role of ischemic gradient in neovascularization of interpolated skin flaps. Arch Otolaryngol Head Neck Surg1996; 122: 886-889.

16. Khouri RK, Brown DM, Leal-Khouri SM, et al. The effect of basic fibroblast growth factor on the neovascularisation process: skin flap survival and staged flap transfers. Br J Plast Surg1991; 44:
585-588.

17. Henry TD, Annex BH, McKendall GR, Azrin MA, Lopez JJ, Giordano FJ, Shah PK, Willerson JT, Benza RL, Berman DS, Gibson CM, Bajamonde A, Rundle AC, Fine J, McCluskey ER. The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation2003; 107:
1359-1365.

18. Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res1999; 85: 221-228.

19. Crosby JR, Kaminski WE, Schatteman G, Martin PJ, Raines EW, Seifert RA, Bowen-Pope DF. Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res2000; 87: 728-730.

20. Rafii S, Lyden D. Therapeutic stem and progenitor cell trans-plantation for organ vascularization and regeneration. Nat Med 2003; 9: 702-712.

21. Planat-Benard V, Silvestre JS, Cousin B, André M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Pénicaud L, Casteilla L. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation2004; 109: 656-663.

22. Evans, M. J., and Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981; 292: 154.

23. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., et al. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145.

24. Friedenstein, A. J. Precursor cells of mechanocytes. Int. Rev. Cytol. 1976; 47: 327.

25. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells2006; 24: 1294-1301.

26. Zhang FG, Tang XF. New advances in the mesenchymal stem cells therapy against skin flaps necrosis. World J Stem Cells2014; 6: 491-496.

27. Behr B, Ko SH, Wong VW, Gurtner GC, Longaker MT. Stem cells. Plast Reconstr Surg2010; 126:
1163-1171.

28. Gir P, Oni G, Brown SA, Mojallal A, Rohrich RJ. Human adipose stem cells: current clinical applications. Plast Reconstr Surg 2012; 129:
1277-1290.

29. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001 Apr; 7(2): 211-28.

30. Becker AJ, McCulloch EA, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963 Feb 2; 197: 452-4.

31. Li GZ, Sun QZ, Xiong ZY, Huang H, Xu J. [The effect of adipose-derived stem cells on viability of random pattern skin flap in rabbits]. Zhonghua zheng xing wai ke za zhi = Zhonghua zhengxing waike zazhi = Chinese journal of plastic surgery. 2011 Mar; 27(2): 119-23.

32. Suartz CV, Gaiba S, França JP, Aloise AC, Ferreira LM. Adipose-derived stem cells (ADSC) in the viability of random skin flap in rats. Acta Cirurgica Brasileira. 2014; 29: 6-9.

33. Hasdemir M, Agir H, Eren GG, Aksu MG, Alagoz MS, Duruksu G, Saglam O, Karaöz E.
Adipose-derived stem cells improve survival of random pattern cutaneous flaps in radiation damaged skin. Journal of Craniofacial Surgery. 2015 Jul 1; 26(5): 1450-5.

34. Reichenberger MA, Heimer S, Schaefer A, Lass U, Gebhard MM, Germann G, Leimer U, Köllensperger E, Mueller W. Adipose derived stem cells protect skin flaps against ischemia-reperfusion injury. Stem Cell Reviews and Reports. 2012 Sep 1; 8(3): 854-62.

35. Izmirli HH, Alagoz MS, Gercek H, Eren GG, Yucel E, Subasi C, Isgoren S, Muezzinoglu B, Karaoz E. Use of Adipose-Derived Mesenchymal Stem Cells to Accelerate Neovascularization in Interpolation Flaps. Journal of Craniofacial Surgery. 2016 Jan 1; 27(1): 264-71.