Effects of rabbit pinna-derived blastema cells on tendon healing

Document Type : Original Article

Authors

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

2 Department of Pharmacy and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran

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

Abstract

Objective(s): Tendon healing is substantially slow and often associated with suboptimal repair. Cell therapy is one of the promising methods to improve tendon repair. Blastema, a population of undifferentiated cells, represents characteristics of pluripotent mesenchymal stem cells and has the potentials to be used in regenerative medicine. The aim of this study was to investigate the use of blastema allotransplantation in rabbit tendon healing.
Materials and Methods: In this study, one rabbit was used as a blastema donor, and twenty-four rabbits were divided into control and treatment groups. Blastema cells were obtained from ear pinna upon punch hole injury in the donor rabbit. Under general anesthesia, a complete transverse tenotomy was performed on the midsubstance of deep digital flexor tendon followed by suture-repair. In the treatment group, 1 × 106 blastema cells suspended in buffer saline were injected intratendinously at the repair site, while the control group received only the buffer saline. Cast coaptation was maintained for two weeks. Eight weeks after the operation, tendons were harvested, and histopathological, biomechanical, and biochemical assays were performed on samples.
Results: Mechanical testing showed a significant increase in ultimate load, energy absorption, stiffness, yield load, stress, and strain in blastema-treated tendons compared to controls. Also, higher hydroxyproline content and improved collagen alignment along with lower inflammatory cell infiltration and decreased angiogenesis were observed in blastema-treated tendons.
Conclusion: Increased levels of hydroxyproline and improved histopathological and biomechanical parameters in the treatment group suggest that blastema cells could be considered an adjunct to tendon repair in rabbits.

Keywords

References

1. Galatz LM, Gerstenfeld L, Heber‐Katz E, Rodeo SA. Tendon regeneration and scar formation: the concept of scarless healing. J Orthop Res 2015; 33:823-831.
2. Longo UG, Lamberti A, Maffulli N, Denaro V. Tissue engineered biological augmentation for tendon healing: a systematic review. Br Med Bull 2010; 98:31-59.
3. Hampson K, Forsyth N, El Haj A, Maffulli N. Tendon tissue engineering. Top Tissue Eng 2008; 4:1-21.
4. Koob TJ. Biomimetic approaches to tendon repair. Comp Biochem Physiol A 2002; 133:1171-1192.
5. Alshomer F, Chaves C, Kalaskar DM. Advances in tendon and ligament tissue engineering: materials perspective. J Mater 2018; Article ID 9868151, 17 pages.
6. Buschmann J, Meier Bürgisser G. Biomechanics of tendons and ligaments. 1st ed. Cambridge, UK; Woodhead Publishing; 2017.p. 251-276.
 7. Mahdavi Shahri N, Naseri F, Kheirabadi M, Babaie S, Azarniya M. The ultra-structural study of blastema in pinna tissues of rabbits with transmission electron microscope. J Biol Sci 2008; 8:933-1000.
8. Tsonis PA. Regenerative biology: the emerging field of tissue repair and restoration. Differentiation 2002; 70:397-409.
9. Brockes JP, Kumar A. Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nature Rev Mol Cell Biol 2002; 3:566-574.
10. Muneoka K, Han M, Gardiner DM. Regriowing human limbs. Sci Am 2008; 298:56-63.
11. Simkin J, Seifert AW. Concise review: translating regenerative biology into clinically relevant therapies: are we on the right path? Stem Cells Transl Med 2018; 7:220-231.
12. Dunk SA. Limb regeneration in humans: micromanaging a plastic environment. Vanderbilt Undergrad Res J 2012; 8:1-4.
13. Simkin J, Sammarco MC, Dawson LA, Schanes PP, Yu L, Muneoka K. The mammalian blastema: regeneration at our fingertips. Regeneration 2015; 2:93-105.
14. Goss RJ, Grimes LN. Epidermal downgrowths in regenerating rabbit ear holes. J Morphol 1975; 146:533-542.
15. Grimes LN, Goss RJ. Regeneration of holes in rabbit ears. Am Zool 1970; 10:537.
16. Williams‐Boyce PK, Daniel JC. Regeneration of rabbit ear tissue. J Exp Zool 1980; 212:243-253.
17. Alizadeh M, Mahdavi N, Rezaeeian S. Histological study of blastema tissue genesis processes, autografted in New Zealand rabbit derm. Med Uni Arak J 2007; 4:55-62. [In Persian]
18. Baghaban Eslaminejad M, Bordbar S. Blastema from rabbit ear contains progenitor cells comparable to marrow derived mesenchymal stem cells. Vet Res Forum 2012; 3:159–165.
19. Baghaban Eslaminejad M, Bordbar S. Isolation and characterization of the progenitor cells from the blastema tissue formed at experimentally-created rabbit ear hole. Iran J Basic Med Sci 2013; 16:109-115.
20. Mahmoudi Z, Moghaddam-Matin M, Saeinasab M, Nakhaei-Rad S, Mirahmadi M, Mahdavi-Shahri N, et al. Blastema cells derived from rabbit ear show stem cell characteristics. J Cell Mol Res 2011; 3:25-31.
21. Javanmard A, Bahrami AR, Mahmoudi Z, Saeinasab M, Mahdavi-Shahri N, Matin MM. Studying the expression patterns of OCT4 and SOX2 proteins in regenerating rabbit ear tissue. World Rabbit Sci 2016; 24:155-164.
22. Saeinasab M, Matin MM, Rassouli FB, Bahrami AR. Blastema cells derived from New Zealand White rabbit’s pinna carry stemness properties as shown by differentiation into insulin producing, neural, and osteogenic lineages representing three embryonic germ layers. Cytotechnology 2016; 68:497-507.
23. Masaki H, Ide H. Regeneration potency of mouse limbs. Dev Growth Differ 2007; 49:89-98.
24. Behfar M, Sarrafzadeh-Rezaei F, Hobbenaghi R, Delirezh N, Dalir-Naghadeh B. Adipose derived stromal vascular fraction improves early tendon healing: an experimental study in rabbits. Vet Res Forum 2011; 2:248-253.
25. Javanmardi S, Sarrafzadeh-Rezaei F, Hobbenaghi R, Dalir-Naghadeh B. Use of undifferentiated cultured bone marrow-derived mesenchymal stem cells for DDF tendon injuries repair in rabbits: a quantitative and qualitative histopathological study. Iran J Vet Surg 2008; 3:51-60.
26.Woessner JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this amino acid. Arch Biochem Biophys 1961; 93:440-447.
27. Gaspar D, Spanoudes K, Holladay C, Pandit A, Zeugolis D. Progress in cell-based therapies for tendon repair. Adv Drug Deliv Rev 2015; 84:240-256.
28. Smith RK, Korda M, Blunn GW, Goodship AE. Isolation and implantation of autologous equine mesenchymal stem cells from bone marrow into the superficial digital flexor tendon as a potential novel treatment. Equine vet J 2003; 35:99-102.
29. Kosaka M, Nakase J, Hayashi K, Tsuchiya H. Adipose-derived regenerative cells promote tendon-bone healing in a rabbit model. Arthroscopy 2016; 32:851-859.
30. Daher RJ, Chahine NO, Razzano P, Patwa SA, Sgaglione NJ, Grande DA. Tendon repair augmented with a novel circulating stem cell population. Int J Clin Exp Med 2011; 4:214-219.
31. Azad-Tirgan M, Sarrafzadeh-Rezaei F, Malekinejad H, Hobbenaghi R, Heshmatian B, Evaluation of tendon healing using fibroblast like synoviocytes in rabbits: a biomechanical study. Vet Res Forum 2016; 7:21-26.
32. Uysal AC, Mizuno H. Tendon regeneration and repair with adipose derived stem cells. Curr Stem Cell Res Ther 2010; 5:161-167.
33. Behfar M, Javanmardi S, Sarrafzadeh-Rezaei F. Comparative Study on functional effects of allotransplantation of bone marrow stromal cells and adipose derived stromal vascular fraction on tendon repair: a biomechanical study in rabbits. Cell J 2014; 16:263-270.
34. Yeung CK, Guo X, Ng YF. Pulsed ultrasound treatment accelerates the repair of Achilles tendon rupture in rats. J Orthop Res 2006; 24:193-201.
35. Witvrouw E, Mahieu N, Roosen P, McNair P. The role of stretching in tendon injuries. Br J Sports Med 2007; 41:224-226.
36. Constantinos N, Maganaris CN, Narici MV. Mechanical properties of tendons. In: Maffulli N, Renström P, Leadbetter WB, editors. Tendon injuries: Basic Science and Clinical Medicine.1st ed. London, UK: Springer 2005.p. 14-21.
37. Dowling B, Dart A. Mechanical and functional properties of the equine superficial digital flexor tendon. Vet J 2005; 170:184-192.
38. Bonifasi‐Lista C, Lakez SP, Small MS, Weiss JA. Viscoelastic properties of the human medial collateral ligament under longitudinal, transverse and shear loading. J Orthop Res 2005; 23:67-76.
39. Wang JH. Mechanobiology of tendon. J Biomech 2006; 39:1563-1582.
40. Mow VC, Huiskes R. Basic orthopaedic biomechanics and mechanobiology. Philadelphia, USA: Lippincott Williams & Wilkins; 2005.p. 301-342.
41. Oryan A, Moshiri A. A long term study on the role of exogenous human recombinant basic fibroblast growth factor on the superficial digital flexor tendon healing in rabbits. J Musculoskelet Neuronal Interact 2011; 11:185-195.
42. Sharma P, Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg 2005; 87:187-202.
43. González-Quevedo D, Martinez-Medina I, Campos A, Campos F, Carriel V. Tissue engineering strategies for the treatment of tendon injuries: a systematic review and meta-analysis of animal models. Bone Joint Res 2018; 7:318-324.
44. Lin Y, Chen X, Yan Z, Liu L, Tang W, Zheng X, et al. Multilineage differentiation of adipose-derived stromal cells from GFP transgenic mice. Mol Cell Biochem 2006; 285:69-78.
45. Gong F, Cui L, Zhang X, Zhan X, Gong X, Wen Y. Piperine ameliorates collagenase-induced Achilles tendon injury in the rat. Connect Tissue Res 2018; 59:21-29.
46. Naderi S, Khayat Zadeh J, Mahdavi Shahri N, Nejad Shahrokh Abady K, Cheravi M, Baharara J, et al. Three-dimensional scaffold from decellularized human gingiva for cell cultures: glycoconjugates and cell behavior. Cell J 2013; 15:166-175.
47. Mahdavi Shahri N, Akbarzadeh Niaki M, Moghadam Matin M, Fereidoni M, Lari R. The histological study of the interactions between rabbit decellularized esophagus scaffold and the blastema tissue obtained from the pinna of New Zealand White rabbit. J Isfahan Med Sch 2014; 31:1865-1875. [In Persian]
48. Dahmardeh T, Mahdavi Shahri N, Moghadam Matin M, Behnam Rassouli M, Lari R. Inducing the effects of acellular dermal matrix on blastema tissue originated from the pinna of New Zealand White rabbit, in vitro. Gene Cell Tissue 2016; 3: e35510.doi: 10.17795/gct-35510.
49. Baharara J, Mahdavishahri N, Saghiri N, Rasti H. Histological study of interaction between blastema tissue and decellularized three-dimensional matrix of bladder. Zahedan J Res Med Sci 2012; 14:8-13.
Iranian Journal of Basic Medical Sciences
Volume 23, Issue 1
January 2020
Pages 13-19

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