Veterinary Research Forum

Histomorphometric and immunohistochemical evaluation of angiogenesis in local ischemia by tissue engineering method in rat: Role of mast cells

Authors

1 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

4 Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

5 Department of Chemical Engineering, Sahand University of Technology, Tabriz, Tabriz, Iran

Abstract

The aim of this study was to find a proper method for improvement of ischemic condition in the rat hind limb and also to observe the efficacy of cell engraftment with alginate/gelatin three-dimensional scaffolds. Eighteen male Wistar rats weighing 200 to 250 g were randomly divided into three groups (n = 6) including a) ischemia group; in which femoral artery was removed after ligation at the distance of 5 mm, b) scaffold group; in which hydrogel scaffold was added to the site of transected femoral artery and c) test group; in which in addition to hydrogel scaffold, mast cells (MCs) were also added (1 × 106 cells). Analysis of capillary density, artery diameter, histomorphometric parameters and immunohistochemistry in transected location were done on day 14 after femoral artery transection. The average number of blood capillary was significantly higher in the test group than other groups. Also, the average number of medium and large blood vessels was significantly higher in the test group compared to ischemia and scaffold groups. Application of MCs through the use of hydrogel scaffolds (alginate/gelatin) can be considered as a new approach in the application of stem cells for therapeutic angiogenesis under ischemic conditions which can improve the angiogenesis process in patients with peripheral artery diseases.

Keywords

Main Subjects

 

  1. Mozaffarian D, Benjamin EJ, Go AS, et al. Executive summary: Heart disease and stroke statistics-2015 update. Circulation 2016; 131(4): 434-441.
  2. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001; 286 (11): 1317-1324.
  3. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation 2006; 113(11): e463-e654.
  4. Niiyama H, Huang NF, Rollins MD, et al. Murine model of hindlimb ischemia. J Vis Exp 2009; 23(1); 1035-1039.
  5. Go AS, Mozaffarian D, Roger VL, et al. Heart and stroke statisticas- 2014 update: A report from the American Heart Association. Circulation 2014; 21; 129(3): e28-e292.
  6. Hobo K, Shimizu T, Sekine H, et al. Therapeutic angiogenesis using tissue engineered human smooth muscle cell sheets. Arterioscler Thromb Vasc Biol2008; 28(4): 637-643.
  7. Lambert MA, Belch JJ. Medical management of critical limb ischemia: Where do we stand today? J Intern Med 2013; 274(4): 295-307.
  8. Wagoner LE, Merrill W, Jacobs J, et al. Angiogenesis protein therapy with human fibroblast growth factor (FGF-1): Results of a phase I open label, dose escalation study in subjects with CAD not eligible for PCI or CABG. Circulation 2007; 116 (16): 443-450.
  9. Sifat AE, Vaidya B, Abbruscato TJ. Blood-brain barrier protection as a therapeutic strategy for acute ischemic stroke. AAPS J 2017; 19(4): 957-972.
  10. Suda M, Shimizu I, Yoshida Y, et al. Peripheral blood mononuclear cells for limb ischemia. In Therapeutic Angiogenesis. Singapore, Singapore: Springer 2017; 25-43.
  11. Hou L, Kim JJ, Woo YJ, et al. Stem cell-based therapies to promote angiogenesis in ischemic cardiovascular disease. Am J Physiol Heart Circ Physiol 2016; 310(4): 455-465.
  12. Hazarika S, Annex BH. Gene and cell therapy for critical limb ischemia. In: Dieter R, Dieter Jr R, Dieter, III R, et al. (Eds). Critical Limb Ischemia. 1st ed. Cham, Switzerland: Springer 2017; 491-501.
  13. Shintani S, Murohara T, Ikeda H, et al. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation 2001; 103(6): 897-903.
  14. Jeon O, Song SJ, Bhang SH, et al. Additive effect of endothelial progenitor cell mobilization and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs. J Biomed Sci 2007; 14(3): 323-330.
  15. Zhang H, Zhang N, Li M, et al. Therapeutic angiogenesis of bone marrow mononuclear cells (MNCs) and peripheral blood MNCs: Transplantation for ischemic hindlimb. Ann Vasc Surg 2008; 22(2): 238-247.
  16. Ribatti D. Mast cells in angiogenesis: The role of angiogenic cytokines. In Biochemical basis and therapeutic implications of angiogenesis. Cham, Switzerland: Springer 2017; 157-167.
  17. Wroblewski M, Velthaus J-L, Bauer R, et al. Effect of MCs on efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme b. J Clin Oncol 2017; 35(15): 11522-11522.
  18. Ribatti D, Ranieri G. Tryptase, a novel angiogenic factor stored in MC granules. Exp Cell Res 2015; 332(2): 157-162.
  19. Norrby K. Mast cells and angiogenesis. APMIS. 2002; 110(5): 355-371.
  20. De Souza Junior DA, Mazucato VM, Santana AC, et al. MCs interact with endothelial cells to accelerate in vitro angiogenesis. Int J Mol Sci 2017; 18(12): 2674.
  21. Lanza R, Langer R, Vacanti JP. Principles of tissue engineering. 4th ed. Boston, USA: Academic Press 2013; 56-112.
  22. Rosellini E, Cristallini C, Barbani N, et al. Preparation and characterization of alginate/gelatin blend films for cardiac tissue engineering. J Biomed Mater Res A 2009; 91(2): 447-453.
  23. Dinescu S, Galateanu B, Radu E, et al. A 3D porous gelatin-alginate-based-IPN acts as an efficient promoter of chondrogenesis from human adipose-derived stem cells. Stem Cells Int 2015; 2015(1):1-17.
  24. Pan T, Song W, Cao X, et al. 3D bioplotting of gelatin/alginate scaffolds for tissue engineering: Influence of crosslinking degree and pore architecture on physicochemical properties. J Mater Sci Technol 2016; 32(9): 889-900.
  25. Luo Y, Lode A, Akkineni AR, et al. Concentrated gelatin/alginate composites for fabrication of predesigned scaffolds with a favorable cell response by 3D plotting. RSC Adv 2015; 5(54): 43480-43488.
  26. Sun G, Zhang X, Shen YI, et al. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proc Natl Acad Sci USA 2011; 108(52): 20976-20981.
  27. Da Silva EZM, Jamur MC, Oliver C. Mast cell function: A new vision of an old cell. J Histochem Cytochem 2014; 62(10): 608-738.
  28. Dahlin JS, Hallgren J. MC progenitors: Origin, development and migration to tissues. Mol Immunol 2015; 63(1): 9-17.
  29. Meurer SK, Neß M, Weiskirchen, et al. Isolation of mature (peritoneum-derived) mast cells and immature (bone marrow-derived) mast cells precursors from mice. PLoS One 2016; 11(6): e0158104.
  30. Mortaz E, Redegeld FA, Nijkamp FP, et al. Dual effects of acetylsalicylic acid on MC degranulation, expression of cyclooxygenase-2 and release of pro-inflammatory cytokines. Biochem Pharmacol 2005; 69(7): 1049-1057.
  31. Bajpai VK, Andreadis ST. Stem cell sources for vascular tissue engineering and regeneration. Tissue Eng Part B Rev 2012; 18(5): 405-425.
  32. Fakoya AO. New delivery systems of stem cells for vascular regeneration in ischemia. Front Cardiovasc Med 2017; 4: 7.
  33. Mortaz E, Givi ME, Da Silva CA, et al. A relation between TGF-β and MC tryptase in experimental emphysema models. Biochim Biophys Acta 2012; 1822(7): 1154-1160.
  34. Vukman KV, Adams PN, Metz M, et al. Fasciola hepatica tegumental coat impairs MCs’ ability to drive Th1 immune responses. J Immunol 2013; 190(6): 2873-2879.
  35. Drew E, Merkens H, Chelliah S, et al. CD34 is a specific marker of mature murine mast cells. Exp Hematol 2002; 30(10): 1211-1218.
  36. Hosseini E, Pedram B, Bahrami AM, et al. Diagnostic procedures for improving of the KIT (CD117) expressed allele burden for the liver metastases from uterus MC tumors: Prognostic value of them etastatic pattern and tumorbiology. Tumour Biol 2015; 36(2): 929-937.
  37. Givi M, Blokhuis B, Da Silva C, et al. Cigarette smoke suppresses the surface expression of c-kit and FcεRI on mast cells. Mediators Inflamm 2013; 2013(1): 1-7.
  38. Cheng Cx, Li Yn, Ohno H, et al. Mast cells appearing in long-term skeletal muscle cell cultures of rat. Anat Rec 2007; 290(11): 1424-1430.
  39. Humason GL. Animal tissue techniques. 4th ed. San Francisco, USA: WH Freeman and Company 1979; 111-131.
  40. Dormandy JA. Management of peripheral arterial disease (PAD). TASC working group. Trans Atlantic Inter-Society Consensus (TASC). J Vasc Surg 2000; 31(1 Pt 2): S1-S296.
  41. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005; 438(7070): 932-936.
  42. Karamysheva A. Mechanisms of angiogenesis. Biochemistry (Mosc) 2008; 73(7): 751-762.
  43. Hamano K, Nishida M, Hirata K, et al. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease. Jap Circ J 2001; 65(9): 845- 847.
  44. Taniyama Y, Morishita R, Aoki M, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindl imb ischemia models: Preclinical study for treatment of peripheral arterial disease. Gene Ther 2001; 8(3): 181-189.
  45. de Vries VC, Pino-Lagos K, Nowak EC, et al. Mast cells condition dendritic cells to mediate allograft tolerance. Immunity 2011; 35(4): 550-561.
  46. Gan PY, Summers SA, Ooi JD, et al. Mast cells contribute to peripheral tolerance and attenuate autoimmune vasculitis. J Am Soc Nephrol 2012; 23(12): 1955-1966.
Veterinary Research Forum

Volume 10, Issue 1
Winter 2019
Page 23-30