1. Hiligsmann M, Cooper C, Arden N, et al. Health economics in the field of osteoarthritis: an expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum 2013; 43: 303–313.
2. Widmer WR, Buckwalter KA, Hill MA, et al. A technique for magnetic resonance imaging of equine cadaver specimens. Vet Radiol Ultrasound 1999; 40: 10–14.
3. Bertone AL, Pittman DD, Bouxsein ML, et al. Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model. J Orthop Res 2004; 22: 1261–1270.
4. Hunziker EB. The elusive path to cartilage regeneration. Adv Mater 2009; 21: 3419–3424.
5. Kreuz PC, Erggelet C, Steinwachs MR, et al. Is microfracture of chondral defects in the knee associated with different results in patients aged 40 years or younger? Arthroscopy 2006; 22: 1180–1186.
6. Kock L, van Donkelaar CC, Ito K. Tissue engineering of functional articular cartilage: the current status. Cell Tissue Res 2012; 347: 613–627.
7. Gorsline RT. Accelerated chondrogenesis in nanofiber polymeric scaffolds embedded with BMP-2 genetically engineered chondrocytes. J Biomed Sci Eng 2010; 3: 908–916.
8. Li W-J, Tuli R, Okafor C, et al. A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials 2005; 26: 599–609.
9. Badylak SF. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol 2004; 12: 367–377.
10. French KM, Boopathy AV, DeQuach JA, et al. A naturally derived cardiac extracellular matrix enhances cardiac progenitor cell behavior in vitro. Acta Biomater 2012; 8: 4357–4364.
11. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials 2011; 32: 3233–3243.
12. Sellaro TL, Ravindra AK, Stolz DB, et al. Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. Tissue Eng 2007; 13: 2301–2310.
13. Sellaro TL, Ranade A, Faulk DM, et al. Maintenance of human hepatocyte function in vitro by liver-derived extracellular matrix gels. Tissue Eng Part A 2010; 16: 1075–1082.
14. Allen RA, Seltz LM, Jiang H, et al. Adrenal extracellular matrix scaffolds support adrenocortical cell proliferation and function in vitro. Tissue Eng Part A 2010; 16: 3363–3374.
15. Zhang Y, He Y, Bharadwaj S, et al. Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype. Biomaterials 2009; 30: 4021–4028.
16. Cortiella J, Niles J, Cantu A, et al. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng Part A 2010; 16: 2565–2580.
17. Brennan EP, Tang XH, Stewart-Akers AM, et al. Chemoattractant activity of degradation products of fetal and adult skin extracellular matrix for keratinocyte progenitor cells. J Tissue Eng Regen Med 2008; 2: 491–498.
18. Crapo PM, Medberry CJ, Reing JE, et al. Biologic scaffolds composed of central nervous system extracellular matrix. Biomaterials 2012; 33: 3539–3547.
19. Beattie AJ, Gilbert TW, Guyot JP, et al. Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. Tissue Eng Part A 2009; 15: 1119–1125.
20. Hutmacher DW. Scaffolds in tissue engineering bone and cartilage. Biomaterials 2000; 21: 2529–2543.
21. Ge Z, Li C, Heng BC, et al. Functional biomaterials for cartilage regeneration. J Biomed Mater Res A 2012; 100: 2526–2536.
22. Brown BN, Badylak SF. Extracellular matrix as an inductive scaffold for functional tissue reconstruction. Transl Res 2014; 163: 268–285.
23. Lee CM, Kisiday JD, McIlwraith CW, et al. Synoviocytes protect cartilage from the effects of injury in vitro. BMC Musculoskelet Disord 2013; 14: 54–68.
24. Ishihara A, Zachos TA, Bartlett JS, et al. Evaluation of permissiveness and cytotoxic effects in equine chondrocytes, synovial cells, and stem cells in response to infection with adenovirus 5 vectors for gene delivery. Am J Vet Res 2006; 67: 1145–1155.
25. Cao L, Yang F, Liu G, et al. The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells. Biomaterials 2011; 32: 3910–3920.
26. Ng VY, Jump SS, Santangelo KS, et al. Genetic engineering of juvenile human chondrocytes improves scaffold-free mosaic neocartilage grafts basic research. Clin Orthop Relat Res 2013; 471: 26–38.
27. Reisbig NA, Hussein HA, Pinnell E, et al. Comparison of four methods for generating decellularized equine synovial extracellular matrix. Am J Vet Res 2016; 77: 1332–1339.
28. Jung DY, Yamada T, Tsuchiya T, et al. Effects of cell-seeding methods of human osteoblast culture on biomechanical properties of porous bioceramic scaffold. Biotechnol Bio-process Eng 2010; 15: 341–348.
29. Faulk DM, Wildemann JD, Badylak SF. Decellularization and cell seeding of whole liver biologic scaffolds composed of extracellular matrix. J Clin Exp Hepatol 2015; 5: 69–80.
30. Rosengren S, Boyle DL, Firestein GS. Acquisition, culture, and phenotyping of synovial fibroblasts. Methods Mol Med 2007; 135: 365–375.
31. Cagnard N, Letourneur F, Essabbani A, et al. Interleukin-32,CCL2,PF4F1 and GFD10 are the only cytokine/chemokine genes differentially expressed by in vitro cultured rheumatoid and osteoarthritis fibroblast-like synoviocytes. Eur Cytokine Netw 2005; 16: 289–292.
32. Seeherman H, Li R, Bouxsein M, et al. rhBMP-2/calcium phosphate matrix accelerates osteotomy-site healing in a nonhuman primate model at multiple treatment times and concentrations. J Bone Joint Surg Am 2006; 88: 144–160.
33. Vanhatupa S, Ojansivu M, Autio R, et al. Bone morphogenetic protein-2 induces donor-dependent osteogenic and adipogenic differentiation in human adipose stem cells. Stem Cells Transl Med 2015; 4: 1391–1402.
34. Soltés L, Mendichi R, Lath D, et al. Molecular characteristics of some commercial high-molecular-weight hyaluronans. Biomed Chromatogr 2002; 16: 459–462.
35. Ranera B, Lyahyai J, Romero A, et al. Immunophenotype and gene expression profiles of cell surface markers of mesenchymal stem cells derived from equine bone marrow and adipose tissue. Vet Immunol Immunopathol 2011; 144: 147–154.
36. Crovace A, Lacitignola L, Rossi G, et al. Histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase-induced tendinitis of equine superficial digital flexor tendon. Vet Med Int 2010;2010:250978.
37. Crosta P. What are stem cells? Medical News Today 2008, updated 2013. Available at: www.medicalnewstoday.com/info/stem_cell. Accessed Mar 3, 2017.
38. Stem cell. The American Heritage new dictionary of cultural literacy. 3rd ed. Available at: www.dictionary.com/browse/stem-celldictionary.com. Accessed Jul 3, 2017.
39. Fan J, Varshney RR, Ren L, et al. Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng Part B Rev 2009; 15: 75–86.
40. De Bari C, Dell'Accio F, Tylzanowski PLFP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 2001; 44: 1928–1942.
41. Fan J, Ren L, Liang R, et al. Chondrogenesis of synovium-derived mesenchymal stem cells in photopolymerizing hydrogel scaffolds. J Biomater Sci Polym Ed 2010; 21: 1653–1667.
42. Sakaguchi Y, Sekiya I, Yagishita K, et al. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 2005; 52: 2521–2529.
43. Fellows CR, Matta C, Zakany R, et al. Adipose, bone marrow and synovial joint-derived mesenchymal stem cells for cartilage repair. Front Genet 2016;7:213.44.
44. Trappmann B, Gautrot JE, Connelly JT, et al. Extracellular-matrix tethering regulates stem-cell fate. Nat Mater 2012; 11: 642–649.
45. Dormond E, Perrier M, Kamen A. From the first to the third generation adenoviral vector: what parameters are governing the production yield? Biotechnol Adv 2009; 27: 133–144.
46. Osago H, Shibata T, Hara N, et al. Quantitative analysis of glycosaminoglycans, chondroitin/dermatan sulfate, hyaluronic acid, heparan sulfate, and keratan sulfate by liquid chromatography-electrospray ionization-tandem mass spectrometry. Anal Biochem 2014; 467: 62–74.
47. Li J, Kim KS, Park JS, et al. BMP-2 and CDMP-2: stimulation of chondrocyte production of proteoglycan. J Orthop Sci 2003; 8: 829–835.
48. Huebsch N, Arany PR, Mao AS, et al. Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater 2010; 9: 518–526.
49. Naito H, Dohi Y, Zimmermann WH, et al. The effect of mesenchymal stem cell osteo-blastic differentiation on the mechanical properties of engineered bone-like tissue. Tissue Eng Part A 2011; 17: 2321–2329.
50. Zachos T, Diggs A, Weisbrode S, et al. Mesenchymal stem cell-mediated gene delivery of bone morphogenetic protein-2 in an articular fracture model. Mol Ther 2007; 15: 1543–1550.
51. Ortved K, Wagner B, Calcedo R, et al. Humoral and cell-mediated immune response, and growth factor synthesis after direct intraarticular injection of rAAV2-IGF-I and rAAV5-IGF-I in the equine middle carpal joint. Hum Gene Ther 2015; 26: 161–171.
52. Goodrich LR, Grieger JC, Phillips JN, et al. scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy. Gene Ther 2015; 22: 536–545.
53. Mardones R, Jofre CM, Tobar L, et al. Mesenchymal stem cell therapy in the treatment of hip osteoarthritis. J Hip Preserv Surg 2017; 4: 159–163.
Advertisement
OBJECTIVE To create a bioactive synovium scaffold by infusing decellularized synovial-derived extracellular matrix (synECM) with synovial-derived mesenchymal stem cells (synMSCs).
SAMPLE Synovium from the femoropatellar and medial femorotibial joints of equine cadavers.
PROCEDURES The synMSCs were cultured in monolayer and not treated or cotransduced to enhance expression of green fluorescent protein (GFP) and human bone morphogenetic protein (BMP)-2. The synECM was decellularized with 0.1% peracetic acid and then seeded with synMSCs (0.5 × 106 cells/0.5 mL) by use of a 30% serum gradient. Samples were evaluated on days 0, 3, 7, and 14. Cell migration, differentiation, and distribution into the synECMs were determined by cell surface marker CD90, viability, histologic morphology, and fluorescence microscopy results and expression of GFP, BMP-2, hyaluronan (HA), and proteoglycan (PG).
RESULTS At day 14, synMSCs were viable and had multiplied 2.5-fold in the synECMs. The synECMs seeded with synMSCs had a significant decrease in CD90 expression and significant increases in HA and PG expression. The synECMs seeded with synMSCs cotransduced with GFP, or BMP-2 had a significant increase in BMP-2 expression.
CONCLUSIONS AND CLINICAL RELEVANCE The synECM seeded with synMSCs or synMSCs cotransduced with GFP, or BMP-2 yielded a bioactive synovial scaffold. Expression of BMP-2 by synMSCs cotransduced to enhance expression of BMP-2 or GFP and an accompanying increase in both HA and PG expression indicated production of anabolic agents and synoviocyte differentiation in the scaffold. Because BMP-2 can promote repair of damaged cartilage, such a bioactive scaffold could be useful for treatment of injured cartilage.