Effect of TGF-β1 transfected dental pulp derived mesenchymal stem cells on in vivo cartilage regeneration | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 6، دوره 28، شماره 11، بهمن 2025، صفحه 1505-1515 اصل مقاله (564.8 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2025.87715.18946 | ||
| نویسندگان | ||
| Betül Tekin Alpargu* 1؛ Saim Ozdamar2؛ Zeynep Burcin Gonen3؛ Ayca Kara4؛ Hasan Salkın5 | ||
| 1Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye | ||
| 2Department of Histology and Embryology, Faculty of Medicine, Pamukkale University, Denizli, Türkiye | ||
| 3Department of Oral and Maxillofacial Surgery, Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Türkiye | ||
| 4Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Türkiye | ||
| 5Department of Histology and Embryology, Faculty of Medicine, Istanbul Beykent University, Istanbul, Türkiye | ||
| چکیده | ||
| Objective(s): This study aimed to investigate the effect of TGF-β1-transfected dental pulp-derived mesenchymal stem cells (DP-MSCs) on the regeneration of osteochondral defects in rabbit knee joints. Materials and Methods: A total of 32 New Zealand white rabbits (3-4 months old, 2-3 kg) were randomly divided into four groups (n=8 per group). Osteochondral defects were surgically created in the distal femoral articular cartilage of three experimental groups, while the control group remained untreated. Group 2 received an intra-articular injection of 0.5 ml sterile saline. Group 3 was administered 0.5 ml of saline containing 3×106 DP-MSCs. Group 4 received 3×106 TGF-β1-transfected DP-MSCs suspended in 0.5 ml of saline. After six weeks, animals were euthanized, and femoral joints were harvested. Tissue sections (5 μm) were analyzed histologically using hematoxylin-eosin, Masson’s trichrome, and Toluidine blue staining, as well as immunohistochemical methods. Results: Histological analysis revealed increased fibrous cartilage in the DP-MSC group compared to the saline group, with some irregular hyaline cartilage regions and dispersed chondrocytes. The TGF-β1+DP-MSC group demonstrated a more significant improvement, characterized by enhanced hyaline cartilage formation and a more organized tissue architecture. Conclusion: TGF-β1 transfection enhances the chondrogenic potential of mesenchymal stem cells by stimulating reparative cellular mechanisms and promoting the formation of hyaline cartilage, thereby facilitating more effective tissue regeneration. These findings suggest that this strategy holds considerable potential for clinical application in cartilage repair and regeneration. | ||
| کلیدواژهها | ||
| Cartilage regeneration؛ Dental pulp؛ Mesenchymal stem cells؛ Osteochondral defects؛ TGF-β1 | ||
| مراجع | ||
|
1. Archer CW, Francis-West P. The chondrocyte. Int J Biochem Cell Biol 2003; 35: 401-404. 2. O’Sullivan J, D’Arcy S, Barry FP, Murphy JM, Coleman CM. Mesenchymal chondroprogenitor cell origin and therapeutic potential. Stem Cell Res Ther 2011; 2: 8-15. 3. Pearle AD, Warren RF, Rodeo SA. Basic science of articular cartilage and osteoarthritis. Clin Sports Med 2005; 24: 1-12. 4. Caldwell KL, Wang J. Cell-based articular cartilage repair: The link between development and regeneration. Osteoarthritis Cartilage 2015; 23: 351-362. 5. Mandai M, Watanabe A, Kurimoto Y, Hirami Y, Morinaga C, Daimon T, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 2017; 376: 1038-1046. 6. Rani S, Ryan AE, Griffin MD, Ritter T. Mesenchymal stem cell-derived extracellular vesicles: Toward cell-free therapeutic applications. Mol Ther 2015; 23: 812-823. 7. Song H, Park KH. Regulation and function of SOX9 during cartilage development and regeneration. Semin Cancer Biol 2020; 67: 12-23. 8. Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther 2008; 10: 223-235. 9. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147. 10. Rizk A, Rabie BM. Electroporation for transfection and differentiation of dental pulp stem cells. Biores Open Access 2013; 2: 155-162. 11. Jiang X, Huang X, Jiang T, Zheng L, Zhao J, Zhang X. The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs). Biomater Sci 2018; 6: 1556-1568. 12. Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 1994; 76: 579-592. 13. Rodas-Junco BA, Canul-Chan M, Rojas-Herrera RA, De-la-Peña C, Nic-Can GI. Stem cells from dental pulp: What epigenetics can do with your tooth. Front Physiol 2017; 8: 999-1019. 14. Lee UL, Jeon SH, Park JY, Choung PH. Effect of platelet-rich plasma on dental stem cells derived from human impacted third molars. Regen Med 2011; 6: 67-79. 15. Salkin H. Effects of TGF-B1-Transfected Pulpal Stem Cells and PRP Application on Chondrogenic Differentiation. Kayseri, Turkey: Erciyes University; 2015. 16. Karsdal MA, Nielsen MJ, Sand JM, Henriksen K, Genovese F, Bay-Jensen AC, et al. Extracellular matrix remodeling: The common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure. Assay Drug Dev Technol 2013; 11: 70-92. 17. Karsdal MA, Bay-Jensen AC, Leeming DJ, Henriksen K, Christiansen C. Quantification of “end products” of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways -- implications for modern clinical chemistry. Biomarkers 2013; 18: 375-378. 18. Kouri JB, Jiménez SA, Quintero M, Chico A. Ultrastructural study of chondrocytes from fibrillated and non-fibrillated human osteoarthritic cartilage. Osteoarthritis Cartilage 1996; 4: 111-125. 19. Morales TI. Chondrocyte moves: Clever strategies? Osteoarthritis Cartilage 2007; 15: 861-871. 20. Harvanová D, Tóthová T, Sarišský M, Amrichová J, Rosocha J. Isolation and characterization of synovial mesenchymal stem cells. Folia Biol (Praha) 2011; 57: 119-124. 21. Jones EA, Crawford A, English A, Henshaw K, Mundy J, Corscadden D, et al. Synovial fluid mesenchymal stem cells in health and early osteoarthritis: Detection and functional evaluation at the single-cell level. Arthritis Rheum 2008; 58: 1731-1740. 22. Iwata H, Ono S, Sato K, Sato T, Kawamura M. Bone morphogenetic protein-induced muscle- and synovium-derived cartilage differentiation in vitro. Clin Orthop Relat Res 1993: 295-300. 23. Zhang S, Muneta T, Morito T, Mochizuki T, Sekiya I. Autologous synovial fluid enhances migration of mesenchymal stem cells from synovium of osteoarthritis patients in tissue culture system. J Orthop Res 2008; 26: 1413-1418. 24. Music E, Futrega K, Doran MR. Sheep as a model for evaluating mesenchymal stem/stromal cell (MSC)-based chondral defect repair. Osteoarthritis Cartilage 2018; 26: 730-740. 25. Riester SM, Denbeigh JM, Lin Y, Jones DL, de Mooij T, Lewallen EA, et al. Safety studies for use of adipose tissue-derived mesenchymal stromal/stem cells in a rabbit model for osteoarthritis to support a phase I clinical trial. Stem Cells Transl Med 2017; 6: 910-922. 26. Castagnini F, Pellegrini C, Perazzo L, Vannini F, Buda R. Joint sparing treatments in early ankle osteoarthritis: current procedures and future perspectives. J Exp Orthop 2016; 3: 3-10. 27. Ryu JS, Jung YH, Cho MY, Yeo JE, Choi YJ, Kim YI, et al. Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes. Biochem Biophys Res Commun 2014; 447: 715-720. 28. Shimomura K, Moriguchi Y, Ando W, Nansai R, Fujie H, Hart DA, et al. Osteochondral repair using a scaffold-free tissue-engineered construct derived from synovial mesenchymal stem cells and a hydroxyapatite-based artificial bone. Tissue Eng Part A 2014; 20: 2291-2304. 29. Karlsson C, Thornemo M, Henriksson HB, Lindahl A. Identification of a stem cell niche in the zone of Ranvier within the knee joint. J Anat 2009; 215: 355-363. 30. Grogan SP, Miyaki S, Asahara H, D’Lima DD, Lotz MK. Mesenchymal progenitor cell markers in human articular cartilage: Normal distribution and changes in osteoarthritis. Arthritis Res Ther 2009; 11: R85-98. 31. Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Moltó F, Nuñez-Córdoba JM, Sánchez-Echenique C, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med 2016; 14: 246-251. 32. Tziafas D. Basic mechanisms of cytodifferentiation and dentinogenesis during dental pulp repair. Int J Dev Biol 1995; 39: 281-290. 33. Rizk A, Rabie AB. Human dental pulp stem cells expressing transforming growth factor β3 transgene for cartilage-like tissue engineering. Cytotherapy 2013; 15: 712-725. 34. Liu P, Sun L, Chen H, Sun S, Zhou D, Pang B, et al. Lentiviral-mediated multiple gene transfer to chondrocytes promotes chondrocyte differentiation and bone formation in rabbit bone marrow-derived mesenchymal stem cells. Oncol Rep 2015; 34: 2618-2626. 35. Tew SR, Clegg PD, Brew CJ, Redmond CM, Hardingham TE. SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis. Arthritis Res Ther 2007; 9: R107-117. 36. Takahashi I, Nuckolls GH, Takahashi K, Tanaka O, Semba I, Dashner R, et al. Compressive force promotes sox9, type II collagen and aggrecan and inhibits IL-1beta expression resulting in chondrogenesis in mouse embryonic limb bud mesenchymal cells. J Cell Sci 1998; 111: 2067-2076. 37. Ikeda T, Kamekura S, Mabuchi A, Kou I, Seki S, Takato T, et al. The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage. Arthritis Rheum 2004; 50: 3561-3573. 38. Bell DM, Leung KK, Wheatley SC, Ng LJ, Zhou S, Ling KW, et al. SOX9 directly regulates the type-II collagen gene. Nat Genet 1997; 16: 174-178. 39. Zeng L, Kempf H, Murtaugh LC, Sato ME, Lassar AB. Shh establishes an Nkx3.2/Sox9 autoregulatory loop that is maintained by BMP signals to induce somitic chondrogenesis. Genes Dev 2002; 16: 1990-2005. | ||
|
آمار تعداد مشاهده مقاله: 426 تعداد دریافت فایل اصل مقاله: 485 |
||