Sıddıka FINDIK, İlker UYAR, Zeynep ALTUNTAŞ, Mehmet Emin Cem YILDIRIM, Serhat YARAR, Murat AKTAN, Ahmet AVCI

The effects of a combination treatment with mesenchymal stem cell and platelet-rich plasma on tendon healing: an experimental study

Background/Aim: The objective of this study was to investigate the effects that the application of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) following tendon repair have on the strength and healing of the tendon and also to examine the possible mechanisms of action that take place. Materials and methods: The Achilles tendons of 80 rats were repaired and divided into eight groups. Following the repairs, MSCs obtained from humans were injected into the rat tendons in groups 1 and 2, a combination of MSCs from humans and PRP from rats was injected into the tendons in groups 3 and 4, and PRP from rats was injected into the tendons in groups 5 and 6. These procedures all took place simultaneously. Groups 7 and 8 did not receive any injections following the repairs. The rats were sacrificed at the end of the first and second months following the procedures, and biomechanical and histopathological analyses were performed. Results: Inflammatory cell density increased most significantly in the combined group when compared to the first and second months. The fibroblast density on the tendon repair region was significantly lower in the second-months groups of each intervention compared to their first-month groups (p = 0.001). For the analysis of the maximum tensile breaking force, the behaviors of the groups over time were significant when compared to the control groups (p = 0.0015). Also, the mean maximum breaking force in the combined group was statistically significantly higher at the end of the second month than at the end of the first month (p = 0.0008). Conclusion: The combination therapy increased tendon strength force. This combination therapy can make a positive contribution to the healing of tendons after surgery.

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1. Andarawis-Puri N, Flatow EL, Soslowsky LJ. Tendon basic science: development, repair, regeneration, and healing. Journal of Orthopaedic Research 2015; 33 (6): 780-784. doi: 10.1002/ jor.22869
2. Wang J, Liao L, Tan J. Mesenchymal-stem-cell-based experimental and clinical trials: current status and open questions. Expert Opinion on Biological Therapy 2011; 11 (7): 893-909. doi: 10.1517/14712598.2011.574119
3. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nature Reviews Immunology 2008; 8 (9): 726-736. doi: 10.1038/nri2395
4. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S et al. Marrowderived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circulation Research 2004; 94 (5): 678-685. doi: 10.1161/01. RES.0000118601.37875.AC
5. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284 (5411): 143-147. doi: 10.1126/ science.284.5411.143
6. Paoloni J, De Vos RJ, Hamilton B, Murrell GA, Orchard J. Plateletrich plasma treatment for ligament and tendon injuries. Clinical Journal of Sport Medicine 2011; 21: 37-45. doi: 10.1097/JSM.0b013e31820758c7
7. Ince B, Yildirim MEC, Dadaci M, Avunduk MC, Savaci N. Comparison of the efficacy of homologous and autologous platelet-rich plasma (PRP) for treating androgenic alopecia. Aesthetic Plastic Surgery 2018; 42 (1): 297-303. doi: 10.1007/ s00266-017-1004-y
8. Rees JD, Maffulli N, Cook J. Management of tendinopathy. The American Journal of Sports Medicine 2009; 37: 1855-67. doi: 10.1177/0363546508324283
9. Yildirim MEC, Ince B, Uyanik O, Okur MI, Dadaci M. Development of hyperalgesia in patients treated with autologous platelet rich plasma due to androgenetic alopecia. Selçuk Tıp Dergisi 2018; 34 (3): 90-93. doi: 10.30733/std.2018.01051
10. Hoffmann A, Gross G. Tendon and ligament engineering in the adult organism: mesenchymal stem cells and gene therapeutic approaches. International Orthopaedics 2007; 31: 791-797. doi: 10.1007/s00264-007-0395-9
11. Bhatia D, Tanner KE, Bonfield W, Citron ND. Factors affecting the strength of flexor tendon repair. The Journal of Hand Surgery: British & European Volume 1992; 17 (5): 550-552. doi: 10.1016/s0266-7681(05)80240-2
12. Lee SY, Kwon B, Lee K, Son YH, Chung SG. Therapeutic mechanisms of human adipose-derived mesenchymal stem cells in a rat tendon injury model. The American Journal of Sports Medicine 2017; 45 (6): 1429-1439. doi: 10.1177/0363546517689874
13. Brunner, E., Domhof, S. and Langer, F. Nonparametric Analysis of Longitudinal Data in Factorial Experiments. NY, USA: Wiley; 2002.
14. Karacor Z, Moran SL. The effect of 5 FU on the expression of transforming growth factor beta-1 (tgf-1) in cultured tendon cells. Acta Medica Anatolia 2014; 4: 138-142. doi: 10.15824/ actamedica.75043
15. Zhao C, Zobitz ME, Sun YL, Predmore KS, Amadio PC et al. Surface treatment with 5-fluorouracil after flexor tendon repair in a canine in vivo model. The Journal of Bone and Joint Surgery 2009; 91 (11): 2673-2682. doi: 10.2106/JBJS.H.01695
16. Zhao C, Chieh HF, Bakri K, Ikeda J, Sun YL et al. The effects of bone marrow stromal cell transplants on tendon healing in vitro. Medical Engineering and Physics 2009; 31 (10): 1271- 1275. doi: 10.1016/j.medengphy.2009.08.004
17. Maruyama M, Wei L, Thio T, Storaci HW, Ueda Y et al. The effect of mesenchymal stem cell sheets on early healing of the achilles tendon in rats. Tissue Engineering, Part A 2020; 26 (3-4): 206- 213. doi: 10.1089/ten.TEA.2019.0163
18. Türkmen F, Özer M, Kaçıra BK, Korucu İH, Göncü G. Bilateral Spontaneous Rupture of Achilles Tendons İn Absence of Risk Factors. Selcuk Medical Journal 2019; 35 (3): 203-206. doi: 10.30733/std.2019.00856 (in Turkish with an abstract in English).
19. Lui PP, Cheuk YC, Hung LK, Fu SC, Chan KM. Increased apoptosis at the late stage of tendon healing. Wound Repair and Regeneration 2007; 15: 702-707. doi: 10.1111/j.1524- 475X.2007.00276.x
20. Hapa O, Cakici H, Gideroğlu K, Ozturan K, Kukner A et al. The effect of ethanol intake on tendon healing: a histological and biomechanical study in a rat model. Archives of Orthopaedic and Trauma Surgery 2009; 129: 1721-1726. doi: 10.1007/s00402-009-0877-x
21. Awad HA, Boivin GP, Dressler MR, Smith FN, Young RG et al. Repair of patellar tendon injuries using a cell-collagen composite. The Journal of Orthopaedic Research 2003; 21: 420- 431. doi: 10.1016/S0736-0266(02)00163-8
22. Chong AK, Ang AD, Goh JC, Hui JH, Lim AY et al. Bone marrowderived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model. The Journal of Bone and Joint Surgery 2007; 89: 74-81. doi: 10.2106/JBJS.E.01396
23. Young RG, Butler DL, Weber W, Caplan AI, Gordon SL et al. Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair. The Journal of Orthopaedic Research 1998; 16: 406-413. doi: 10.1002/jor.1100160403
24. Uysal C, Tobita M, Hyakusoku H, Mizuno H. Adipose-derived stem cells enhance primary tendon repair: biomechanical and immunohistochemical evaluation. Journal of Plastic, Reconstructive and Aesthetic Surgery 2012; 65 (12): 1712- 1719. doi: 10.1016/j.bjps.2012.06.011
25. Yuksel S, Guleç MA, Gultekin MZ, Adanır O, Caglar A et al. Comparison of the early period effects of bone marrowderived mesenchymal stem cells and platelet-rich plasma on the achilles tendon ruptures in rats. Connective Tissue Research 2016; 57 (5): 360-373. doi: 10.1080/03008207.2016.1189909
26. Martinello T, Bronzini I, Perazzi A, Testoni S, De Benedictis GM et al. Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platelet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep. The Journal of Orthopaedic Research 2013; 31 (2): 306-314. doi: 10.1002/jor.22205