Comprehensive analysis of culture conditions governing differentiation of MSCs into articular chondrocytes

Papers of special note have been highlighted as: • of interest

References

• 1. Liu Y, Shah KM, Luo J. Strategies for Articular Cartilage Repair and Regeneration. Front. Bioengin. Biotechnol. 9, 770655 (2021).
  MedlineGoogle Scholar
• 2. Grenier S, Bhargava MM, Torzilli PA. An in vitro model for the pathological degradation of articular cartilage in osteoarthritis. J. Biomech. 47(3), 645–652 (2014).
  MedlineGoogle Scholar
• 3. Carey JL. Fibrocartilage Following Microfracture Is Not as Robust as Native Articular Cartilage. J. Bone Joint Surg. 94(11), e80 (2012).
  MedlineGoogle Scholar
• 4. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat. Revt. Rheumatolt. 11(1), 21–34 (2015). • Provides a comprehensive analysis of the advantages and disadvantages of conventional therapies used for the treatment of osteoarthritis.
  Medline CASGoogle Scholar
• 5. Bert JM. Abandoning Microfracture of the Knee: Has the Time Come? Arthroscopy: The Journal of Arthroscopic & Related Surgery 31(3), 501–505 (2015).
  MedlineGoogle Scholar
• 6. Bark S, Piontek T, Behrens P, Mkalaluh S, Varoga D, Gille J. Enhanced microfracture techniques in cartilage knee surgery: fact or fiction? World Jt Orthopt. 5(4), 444–449 (2014).
  MedlineGoogle Scholar
• 7. Patil S, Tapasvi SR. Osteochondral autografts. Current Reviews in Musculoskeletal Medicine 8(4), 423–428 (2015).
  MedlineGoogle Scholar
• 8. Ahmad J, Jones K. Comparison of Osteochondral Autografts and Allografts for Treatment of Recurrent or Large Talar Osteochondral Lesions. Foot & Ankle International 37(1), 40–50 (2016).
  MedlineGoogle Scholar
• 9. Cook JL, Stannard JP, Stoker AM et al. Importance of Donor Chondrocyte Viability for Osteochondral Allografts. Am. J. Sports Med. 44(5), 1260–1268 (2016).
  MedlineGoogle Scholar
• 10. Baldwin P, Li DJ, Auston DA, Mir HS, Yoon RS, Koval KJ. Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery. J. Orthop. Trauma 33(4), 203–213 (2019).
  MedlineGoogle Scholar
• 11. Mistry H, Connock M, Pink J et al. Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. Health Technol. Assess. 21(6), 1–294 (2017).
  Google Scholar
• 12. Harris JD, Siston RA, Brophy RH, Lattermann C, Carey JL, Flanigan DC. Failures, re-operations, and complications after autologous chondrocyte implantation – a systematic review. Osteoarthritis Cartilage 19(7), 779–791 (2011).
  Medline CASGoogle Scholar
• 13. Davies RL, Kuiper NJ. Regenerative Medicine: A Review of the Evolution of Autologous Chondrocyte Implantation (ACI) Therapy. Bioengineering 6(1), 22 (2019).
  Medline CASGoogle Scholar
• 14. Welch T, Mandelbaum B, Tom M. Autologous Chondrocyte Implantation: Past, Present, and Future. Sports Medt. Arthrosct. Revt. 24(2), 85–91 (2016).
  MedlineGoogle Scholar
• 15. Caplan AI. Mesenchymal stem cells. J. Orthop. Res. 9(5), 641–650 (1991). • Caplan is recognized as a pioneering figure in the field of stem cell research, and his seminal paper in which he first described mesenchymal stem cells represents a significant milestone in the field.
  Medline CASGoogle Scholar
• 16. Orbay H, Tobita M, Mizuno H. Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications. Stem Cells Intt. 2012, 461718–461718 (2012).
  MedlineGoogle Scholar
• 17. Xu L, Li G. Circulating mesenchymal stem cells and their clinical implications. Journal of Orthopaedic Translation 2(1), 1–7 (2014).
  Google Scholar
• 18. Becker AJ, Mcculloch EA, Till JE. Cytological Demonstration of the Clonal Nature of Spleen Colonies Derived from Transplanted Mouse Marrow Cells. Nature 197(4866), 452–454 (1963).
  Medline CASGoogle Scholar
• 19. Siminovitch L, Mcculloch EA, Till JE. The distribution of colony-forming cells among spleen colonies. Journal of Cellular and Comparative Physiology 62(3), 327–336 (1963).
  Medline CASGoogle Scholar
• 20. Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif. 3(4), 393–403 (1970).
  CASGoogle Scholar
• 21. Friedenstein AJ, Deriglasova UF, Kulagina NN et al. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp. Hematol. 2(2), 83–92 (1974).
  Medline CASGoogle Scholar
• 22. Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4), 315–317 (2006).
  Medline CASGoogle Scholar
• 23. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells – current trends and future prospective. Biosci. Rep. 35(2), e00191 (2015).
  MedlineGoogle Scholar
• 24. Nitzsche F, Müller C, Lukomska B, Jolkkonen J, Deten A, Boltze J. Concise review: MSC adhesion cascade-insights into homing and transendothelial migration. Stem Cells 35(6), 1446–1460 (2017).
  MedlineGoogle Scholar
• 25. Ullah M, Liu DD, Thakor AS. Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement. iScience 15, 421–438 (2019).
  Medline CASGoogle Scholar
• 26. Bobis-Wozowicz S, Miekus K, Wybieralska E et al. Genetically modified adipose tissue-derived mesenchymal stem cells overexpressing CXCR4 display increased motility, invasiveness, and homing to bone marrow of NOD/SCID mice. Exp. Hematol. 39(6), 686–696; e684 (2011).
  Medline CASGoogle Scholar
• 27. Shao Y, Zhou F, He D, Zhang L, Shen J. Overexpression of CXCR7 promotes mesenchymal stem cells to repair phosgene-induced acute lung injury in rats. Biomedicine & Pharmacotherapy 109, 1233–1239 (2019).
  Medline CASGoogle Scholar
• 28. Lin T-H, Liu H-H, Tsai T-H et al. CCL2 increases αvβ3 integrin expression and subsequently promotes prostate cancer migration. Biochimica et Biophysica Acta (BBA)-General Subjects 1830(10), 4917–4927 (2013).
  CASGoogle Scholar
• 29. Muller WA. Mechanisms of leukocyte transendothelial migration. Annual Review of Pathology: Mechanisms of Disease 6, 323–344 (2011).
  CASGoogle Scholar
• 30. Bi L K, Zhou N, Liu C et al. Kidney cancer cells secrete IL-8 to activate Akt and promote migration of mesenchymal stem cells. Urologic oncology 32(5), 607–612 (2014).
  Medline CASGoogle Scholar
• 31. Bayo J, Real A, Fiore EJ et al. IL-8, GRO and MCP-1 produced by hepatocellular carcinoma microenvironment determine the migratory capacity of human bone marrow-derived mesenchymal stromal cells without affecting tumor aggressiveness. Oncotarget 8(46), 80235 (2017).
  MedlineGoogle Scholar
• 32. Scarfe L, Taylor A, Sharkey J et al. Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration. Stem Cell Research & Therapy 9(1), 1–17 (2018).
  MedlineGoogle Scholar
• 33. Chen W, Li M, Cheng H et al. Overexpression of the mesenchymal stem cell Cxcr4 gene in irradiated mice increases the homing capacity of these cells. Cell Biochem. Biophys. 67, 1181–1191 (2013).
  Medline CASGoogle Scholar
• 34. Chen Z, Chen Q, Du H, Xu L, Wan J. Mesenchymal stem cells and CXC chemokine receptor 4 overexpression improved the therapeutic effect on colitis via mucosa repair. Experimental and Therapeutic Medicine 16(2), 821–829 (2018).
  MedlineGoogle Scholar
• 35. Cui L-L, Nitzsche F, Pryazhnikov E et al. Integrin α4 overexpression on rat mesenchymal stem cells enhances transmigration and reduces cerebral embolism after intracarotid injection. Stroke 48(10), 2895–2900 (2017).
  Medline CASGoogle Scholar
• 36. Rustad KC, Gurtner GC. Mesenchymal Stem Cells Home to Sites of Injury and Inflammation. Advt. Wound Care (New Rochelle) 1(4), 147–152 (2012).
  MedlineGoogle Scholar
• 37. Yan X-Z, Van Den Beucken JJJP, Both SK, Yang P-S, Jansen JA, Yang F. Biomaterial Strategies for Stem Cell Maintenance During In Vitro Expansion. Tissue Engineering Part B: Reviews 20(4), 340–354 (2013).
  MedlineGoogle Scholar
• 38. Bunpetch V, Zhang Z-Y, Zhang X et al. Strategies for MSC expansion and MSC-based microtissue for bone regeneration. Biomaterials 196, 67–79 (2019).
  Medline CASGoogle Scholar
• 39. Steens J, Klein D. Current Strategies to Generate Human Mesenchymal Stem Cells In Vitro. Stem Cells Int. 2018, 6726185 (2018).
  MedlineGoogle Scholar
• 40. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue. Stem Cells 24(5), 1294–1301 (2006).
  Medline CASGoogle Scholar
• 41. Stewart MC, Stewart AA. Mesenchymal stem cells: characteristics, sources, and mechanisms of action. Vet. Clin. North Am. Equine Prac. 27(2), 243–261 (2011).
  MedlineGoogle Scholar
• 42. Brown C, Mckee C, Bakshi S et al. Mesenchymal stem cells: cell therapy and regeneration potential. J. Tissue Eng. Regen. Med. 13(9), 1738–1755 (2019).
  Medline CASGoogle Scholar
• 43. Huang GT, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J. Dent. Res. 88(9), 792–806 (2009).
  Medline CASGoogle Scholar
• 44. Sharpe PT. Dental mesenchymal stem cells. Development 143(13), 2273–2280 (2016).
  Medline CASGoogle Scholar
• 45. Tomar GB, Srivastava RK, Gupta N et al. Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem. Biophys. Res. Commun. 393(3), 377–383 (2010).
  Medline CASGoogle Scholar
• 46. Li C-Y, Wu X-Y, Tong J-B et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Research & Therapy 6(1), 55 (2015).
  MedlineGoogle Scholar
• 47. Gale AL, Linardi RL, Mcclung G, Mammone RM, Ortved KF. Comparison of the chondrogenic differentiation potential of equine synovial membrane-derived and bone marrow-derived mesenchymal stem cells. Frontiers in Veterinary Science 6(JUN), 1–10 (2019).
  MedlineGoogle Scholar
• 48. Ciuffreda MC, Malpasso G, Musarò P, Turco V, Protocols for in vitro Differentiation of Human Mesenchymal Stem Cells into Osteogenic, Chondrogenic and Adipogenic Lineages. In: Mesenchymal Stem Cells: Methods and Protocols. Gnecchi M (Ed.). Springer, NY, USA, 149–158 (2016).
  Google Scholar
• 49. Nejadnik H, Diecke S, Lenkov OD et al. Improved Approach for Chondrogenic Differentiation of Human Induced Pluripotent Stem Cells. Stem Cell Reviews and Reports 11(2), 242–253 (2015).
  Medline CASGoogle Scholar
• 50. Lavrentieva A, Hatlapatka T, Neumann A, Weyand B, Kasper C. Potential for osteogenic and chondrogenic differentiation of MSC. Adv. Biochem. Eng. Biotechnol. 129, 73–88 (2013).
  Medline CASGoogle Scholar
• 51. Seifert A, Werheid DF, Knapp SM, Tobiasch E. Role of Hox genes in stem cell differentiation. World J. Stem Cells 7(3), 583–595 (2015).
  MedlineGoogle Scholar
• 52. Guérit D, Brondello J-M, Chuchana P et al. FOXO3A Regulation by miRNA-29a Controls Chondrogenic Differentiation of Mesenchymal Stem Cells and Cartilage Formation. Stem Cells and Development 23(11), 1195–1205 (2014).
  Medline CASGoogle Scholar
• 53. Almalki SG, Agrawal DK. Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation 92(1-2), 41–51 (2016). • The authors of this article have provided an in-depth explanation of the molecular mechanisms underlying the trilineage differentiation of mesenchymal stem cells (MSCs).
  Medline CASGoogle Scholar
• 54. Lampert F, Kütscher C, Stark G, Finkenzeller G. Overexpression of Hif-1α in mesenchymal stem cells affects cell-autonomous Angiogenic and osteogenic parameters. J. Cell. Biochem. 117(3), 760–768 (2016).
  Medline CASGoogle Scholar
• 55. Gao RT, Zhan LP, Meng C et al. Homeobox B7 promotes the osteogenic differentiation potential of mesenchymal stem cells by activating RUNX2 and transcript of BSP. Int. J. Clin. Exp. Med. 8(7), 10459–10470 (2015).
  MedlineGoogle Scholar
• 56. Varela N, Aranguiz A, Lizama C et al. Mitotic inheritance of mRNA facilitates translational activation of the osteogenic-Lineage commitment factor runx2 in progeny of osteoblastic cells. J. Cell. Physiol. 231(5), 1001–1014 (2016).
  Medline CASGoogle Scholar
• 57. Han S-M, Han S-H, Coh Y-R et al. Enhanced proliferation and differentiation of Oct4- and Sox2-overexpressing human adipose tissue mesenchymal stem cells. Experimental & Molecular Medicine 46(6), e101 (2014).
  Medline CASGoogle Scholar
• 58. Alexander PG, Gottardi R, Lin H, Lozito TP, Tuan RS. Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases. Experimental Biology and Medicine 239(9), 1080–1095 (2014).
  Google Scholar
• 59. Yeung P, Cheng KH, Yan CH, Chan BP. Collagen microsphere based 3D culture system for human osteoarthritis chondrocytes (hOACs). Scientific Reports 9(1), 1–14 (2019).
  MedlineGoogle Scholar
• 60. Liu Z, Tang M, Zhao J, Chai R, Kang J. Looking into the Future: Toward Advanced 3D Biomaterials for Stem-Cell-Based Regenerative Medicine. Adv. Mater. 30(17), e1705388 (2018).
  MedlineGoogle Scholar
• 61. Velasco MA, Narváez-Tovar CA, Garzón-Alvarado DA. Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering. Bio. Med. Research International 2015, 1–21 (2015).
  Google Scholar
• 62. Jensen C, Teng Y. Is It Time to Start Transitioning From 2D to 3D Cell Culture? Frontiers in Molecular Biosciences 7, 33 (2020).
  Medline CASGoogle Scholar
• 63. Ravi M, Paramesh V, Kaviya SR, Anuradha E, Solomon FDP. 3D Cell Culture Systems: Advantages and Applications. J. Cell. Physiol. 230(1), 16–26 (2015).
  Medline CASGoogle Scholar
• 64. Rubí-Sans G et al. Development of a Three-Dimensional Bioengineered Platform for Articular Cartilage Regeneration. Biomolecules. 10 (2019).
  MedlineGoogle Scholar
• 65. Zhou F et al. Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair. Acta Biomaterialia. 63, 64–75 (2017).
  Medline CASGoogle Scholar
• 66. Morille M, Toupet K, Montero-Menei CN, Jorgensen C, Noël D. PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis. Biomaterials 88, 60–69 (2016).
  Medline CASGoogle Scholar
• 67. Park K-S et al. Versatile effects of magnesium hydroxide nanoparticles in PLGA scaffold–mediated chondrogenesis. Acta Biomaterialia. 73, 204–216 (2018).
  Medline CASGoogle Scholar
• 68. Ahmed M et al. A combinatorial approach towards the design of nanofibrous scaffolds for chondrogenesis. Scientific Reports. 5(1), 14804 (2015).
  Medline CASGoogle Scholar
• 69. Tamaddon M et al. Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro. Scientific Reports. 7(1), 43519 (2017).
  Medline CASGoogle Scholar
• 70. Merlin Rajesh Lal LP, Suraishkumar GK, Nair PD. Chitosan-agarose scaffolds supports chondrogenesis of Human Wharton's Jelly mesenchymal stem cells. J. Biomedical Mat. Res. Part A. 105(7), 1845–1855 (2017).
  MedlineGoogle Scholar
• 71. Prasopthum A et al. Three dimensional printed degradable and conductive polymer scaffolds promote chondrogenic differentiation of chondroprogenitor cells. Biomat. Sci. 8(15), 4287–4298 (2020).
  CASGoogle Scholar
• 72. Man Z et al. The effects of co-delivery of BMSC-affinity peptide and rhTGF-β1 from coaxial electrospun scaffolds on chondrogenic differentiation. Biomaterials. 35(19), 5250–5260 (2014).
  Medline CASGoogle Scholar
• 73. Brunelle AR et al. Electrospun thermosensitive hydrogel scaffold for enhanced chondrogenesis of human mesenchymal stem cells. Acta Biomaterialia. 66, 166–176 (2018).
  Medline CASGoogle Scholar
• 74. NG H, Lee K-X, Shen Y-F. Articular Cartilage: Structure, Composition, Injuries and Repair. JSM Bone and Joint Dis. 1(2), 1010 (2017).
  Google Scholar
• 75. Nava MM, Draghi L, Giordano C, Pietrabissa R. The Effect of Scaffold Pore Size in Cartilage Tissue Engineering. Journal of Applied Biomaterials & Functional Materials 14(3), e223–e229 (2016).
  Medline CASGoogle Scholar
• 76. BruŽauskaitė I, Bironaitė D, Bagdonas E, Bernotienė E. Scaffolds and cells for tissue regeneration: different scaffold pore sizes–different cell effects. Cytotechnology 68(3), 355–369 (2016).
  Medline CASGoogle Scholar
• 77. Jafari M, Paknejad Z, Rad MR et al. Polymeric scaffolds in tissue engineering: a literature review. Journal of Biomedical Materials Research Part B: Applied Biomaterials 105(2), 431–459 (2017).
  Medline CASGoogle Scholar
• 78. Correia SI, Pereira H, Silva-Correia J et al. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint. Journal of The Royal Society Interface 11(92), 20130784–20130784 (2014).
  Medline CASGoogle Scholar
• 79. Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: a review. Bioactive Materials 4, 271–292 (2019).
  MedlineGoogle Scholar
• 80. Deepthi S, Jayakumar R. Prolonged release of TGF-β from polyelectrolyte nanoparticle loaded macroporous chitin-poly(caprolactone) scaffold for chondrogenesis. International Journal of Biological Macromolecules 93, 1402–1409 (2016).
  Medline CASGoogle Scholar
• 81. Almeida HV, Eswaramoorthy R, Cunniffe GM, Buckley CT, O'brien FJ, Kelly DJ. Fibrin hydrogels functionalized with cartilage extracellular matrix and incorporating freshly isolated stromal cells as an injectable for cartilage regeneration. Acta Biomaterialia 36, 55–62 (2016).
  Medline CASGoogle Scholar
• 82. Levorson EJ, Santoro M, Kasper FK, Mikos AG. Direct and indirect co-culture of chondrocytes and mesenchymal stem cells for the generation of polymer/extracellular matrix hybrid constructs. Acta Biomater. 10(5), 1824–1835 (2014).
  Medline CASGoogle Scholar
• 83. Marchan J, Wittig O, Diaz-Solano D, Gomez M, Cardier JE. Enhanced chondrogenesis from chondrocytes co-cultured on mesenchymal stromal cells: implication for cartilage repair. Injury 53(2), 399–407 (2022).
  MedlineGoogle Scholar
• 84. Acharya C, Adesida A, Zajac P et al. Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation. J. Cell. Physiol. 227(1), 88–97 (2012).
  Medline CASGoogle Scholar
• 85. Markway BD, Tan G-K, Brooke G, Hudson JE, Cooper-White JJ, Doran MR. Enhanced Chondrogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells in Low Oxygen Environment Micropellet Cultures. Cell Transplant. 19(1), 29–42 (2010).
  MedlineGoogle Scholar
• 86. Pattappa G, Johnstone B, Zellner J, Docheva D, Angele P. The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response. International Journal of Molecular Sciences 20(3), 484 (2019).
  Medline CASGoogle Scholar
• 87. Leijten J, Georgi N, Moreira Teixeira L, Van Blitterswijk CA, Post JN, Karperien M. Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate. Proceedings of the National Academy of Sciences 111(38), 13954–13959 (2014).
  Medline CASGoogle Scholar
• 88. Anderson DE, Markway BD, Bond D, Mccarthy HE, Johnstone B. Responses to altered oxygen tension are distinct between human stem cells of high and low chondrogenic capacity. Stem Cell Research & Therapy 7(1), 154 (2016). • The role of oxygen concentration in the differentiation of MSCs into chondrocytes was described in great detail in this article.
  MedlineGoogle Scholar
• 89. Shang J, Liu H, Li J, Zhou Y. Roles of hypoxia during the chondrogenic differentiation of mesenchymal stem cells. Curr. Stem Cell Res. Ther. 9(2), 141–147 (2014).
  Medline CASGoogle Scholar
• 90. Glatt V, Evans CH, Stoddart MJ. Regenerative rehabilitation: the role of mechanotransduction in orthopaedic regenerative medicine. J. Orthop. Res. 37(6), 1263–1269 (2019).
  MedlineGoogle Scholar
• 91. Vaca-González JJ, Guevara JM, Moncayo MA, Castro-Abril H, Hata Y, Garzón-Alvarado DA. Biophysical Stimuli: A Review of Electrical and Mechanical Stimulation in Hyaline Cartilage. Cartilage 10(2), 157–172 (2017).
  MedlineGoogle Scholar
• 92. Gaut C, Sugaya K. Critical review on the physical and mechanical factors involved in tissue engineering of cartilage. Regenerative Medicine 10(5), 665–679 (2015).
  CASGoogle Scholar
• 93. Zhang S, Yao Y. The Role of Mechanical Regulation in Cartilage Tissue Engineering. Curr. Stem Cell Res. Ther. 16(8), 939–948 (2021).
  Medline CASGoogle Scholar
• 94. Hodder E, Guppy F, Covill D, Bush P. The effect of hydrostatic pressure on proteoglycan production in articular cartilage in vitro: a meta-analysis. Osteoarthritis Cartilage 28(8), 1007–1019 (2020).
  Medline CASGoogle Scholar
• 95. Pattappa G, Zellner J, Johnstone B, Docheva D, Angele P. Cells under pressure-the relationship between hydrostatic pressure and mesenchymal stem cell chondrogenesis. eCells & Materials 2019(37), 360–381 (2019).
  Google Scholar
• 96. Duraine GD, Athanasiou KA. ERK activation is required for hydrostatic pressure-induced tensile changes in engineered articular cartilage. Journal of Tissue Engineering and Regenerative Medicine 9(4), 368–374 (2015).
  Medline CASGoogle Scholar
• 97. Steward A, Kelly D, Wagner D. The role of calcium signalling in the chondrogenic response of mesenchymal stem cells to hydrostatic pressure. Eur. Cell Mater. 28, 358–371 (2014).
  Medline CASGoogle Scholar
• 98. Hosseini M-S, Tafazzoli-Shadpour M, Haghighipour N, Aghdami N, Goodarzi A. The Synergistic Effects of Shear Stress and Cyclic Hydrostatic Pressure Modulate Chondrogenic Induction of Human Mesenchymal Stem Cells. The International Journal of Artificial Organs 38(10), 557–564 (2015).
  Medline CASGoogle Scholar
• 99. Fini M, Pagani S, Giavaresi G et al. Functional tissue engineering in articular cartilage repair: is there a role for electromagnetic biophysical stimulation? Tissue Engineering Part B: Reviews 19(4), 353–367 (2013).
  Medline CASGoogle Scholar
• 100. Murphy MP, Koepke LS, Lopez MT et al. Articular cartilage regeneration by activated skeletal stem cells. Nat. Med. 26(10), 1583–1592 (2020).
  Medline CASGoogle Scholar
• 101. Chau M, Dou Z, Baroncelli M et al. The synovial microenvironment suppresses chondrocyte hypertrophy and promotes articular chondrocyte differentiation. NPJ Regen. Med. 7(1), 51 (2022).
  Medline CASGoogle Scholar
• 102. Augustyniak E, Trzeciak T, Richter M, Kaczmarczyk J, Suchorska W. The role of growth factors in stem cell-directed chondrogenesis: a real hope for damaged cartilage regeneration. International Orthopaedics 39(5), 995–1003 (2015). • The authors of this article have provided an extensive explanation of the contribution of growth factors in the process of chondrogenesis.
  MedlineGoogle Scholar
• 103. Coricor G, Serra R. TGF-β regulates phosphorylation and stabilization of Sox9 protein in chondrocytes through p38 and Smad dependent mechanisms. Scientific Reports 6(1), 38616 (2016).
  Medline CASGoogle Scholar
• 104. Wang W, Rigueur D, Lyons KM. TGFβ signaling in cartilage development and maintenance. Birth Defects Res. C Embryo Today 102(1), 37–51 (2014).
  Medline CASGoogle Scholar
• 105. Thielen NGM, Van Der Kraan PM, Van Caam APM. TGFβ/BMP Signaling Pathway in Cartilage Homeostasis. Cells 8(9), 969 (2019).
  Medline CASGoogle Scholar
• 106. Zhou N, Li Q, Lin X et al. BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells. Cell Tissue Res. 366(1), 101–111 (2016).
  Medline CASGoogle Scholar
• 107. Jang Y, Jung H, Nam Y et al. Centrifugal gravity-induced BMP4 induces chondrogenic differentiation of adipose-derived stem cells via SOX9 upregulation. Stem Cell Research & Therapy 7(1), 184 (2016).
  MedlineGoogle Scholar
• 108. Kayabaşi GK, Tiğli Aydin RS, Gümüşderelioğlu M. In vitro chondrogenesis by BMP6 gene therapy. Journal of Biomedical Materials Research Part A 101A(5), 1353–1361 (2013).
  CASGoogle Scholar
• 109. Huang X, Zhong L, Post JN, Karperien M. Co-treatment of TGF-β3 and BMP7 is superior in stimulating chondrocyte redifferentiation in both hypoxia and normoxia compared to single treatments. Scientific Reports 8(1), 10251 (2018).
  MedlineGoogle Scholar
• 110. Iwakura T, Sakata R, Reddi AH. Induction of Chondrogenesis and Expression of Superficial Zone Protein in Synovial Explants with TGF-β1 and BMP-7. Tissue Engineering Part A 19(23-24), 2638–2644 (2013).
  Medline CASGoogle Scholar
• 111. Cheng A, Gustafson AR, Schaner Tooley CE, Zhang M. BMP-9 dependent pathways required for the chondrogenic differentiation of pluripotent stem cells. Differentiation 92(5), 298–305 (2016).
  Medline CASGoogle Scholar
• 112. Liu X, Du M, Wang Y, Liu S, Liu X. BMP9 overexpressing adipose-derived mesenchymal stem cells promote cartilage repair in osteoarthritis-affected knee joint via the Notch1/Jagged1 signaling pathway. Exp. Ther. Med. 16(6), 4623–4631 (2018).
  Medline CASGoogle Scholar
• 113. Morgan BJ, Bauza-Mayol G, Gardner OFW et al. Bone Morphogenetic Protein-9 Is a Potent Chondrogenic and Morphogenic Factor for Articular Cartilage Chondroprogenitors. Stem Cells and Development 29(14), 882–894 (2020).
  Medline CASGoogle Scholar
• 114. Cleary MA, Van Osch GJVM, Brama PA, Hellingman CA, Narcisi R. FGF, TGFβ and Wnt crosstalk: embryonic to in vitro cartilage development from mesenchymal stem cells. Journal of Tissue Engineering and Regenerative Medicine 9(4), 332–342 (2015).
  Medline CASGoogle Scholar
• 115. Praul CA, Ford BC, Leach RM. Effect of fibroblast growth factors 1, 2, 4, 5, 6, 7, 8, 9, and 10 on avian chondrocyte proliferation. J. Cell. Biochem. 84(2), 359–366 (2002).
  MedlineGoogle Scholar
• 116. Nasrabadi D, Rezaeiani S, Eslaminejad MB, Shabani A. Improved Protocol for Chondrogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells-Effect of PTHrP and FGF-2 on TGFβ1/BMP2-Induced Chondrocytes Hypertrophy. Stem Cell Reviews and Reports 14(5), 755–766 (2018).
  Medline CASGoogle Scholar
• 117. Huang L, Yi L, Zhang C et al. Synergistic Effects of FGF-18 and TGF-β3 on the Chondrogenesis of Human Adipose-Derived Mesenchymal Stem Cells in the Pellet Culture. Stem Cells Int. 2018, 7139485 (2018).
  MedlineGoogle Scholar
• 118. Correa D, Somoza RA, Lin P et al. Sequential exposure to fibroblast growth factors (FGF) 2, 9 and 18 enhances hMSC chondrogenic differentiation. Osteoarthritis Cartilage 23(3), 443–453 (2015).
  Medline CASGoogle Scholar
• 119. Kwon H, Paschos NK, Hu JC, Athanasiou K. Articular cartilage tissue engineering: the role of signaling molecules. Cell. Mol. Life Sci. 73(6), 1173–1194 (2016).
  Medline CASGoogle Scholar
• 120. Demoor M, Ollitrault D, Gomez-Leduc T et al. Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction. Biochimica et Biophysica Acta (BBA)-General Subjects 1840(8), 2414–2440 (2014).
  CASGoogle Scholar
• 121. Wen C, Xu L, Xu X, Wang D, Liang Y, Duan L. Insulin-like growth factor-1 in articular cartilage repair for osteoarthritis treatment. Arthritis Research & Therapy 23(1), 277 (2021).
  Medline CASGoogle Scholar
• 122. Widowati W, Afifah E, Mozef T et al. Effects of insulin-like growth factor-induced Wharton jelly mesenchymal stem cells toward chondrogenesis in an osteoarthritis model. Iran J. Basic Med. Sci. 21(7), 745–752 (2018).
  MedlineGoogle Scholar
• 123. Li T, Liu B, Chen K, Lou Y, Jiang Y, Zhang D. Small molecule compounds promote the proliferation of chondrocytes and chondrogenic differentiation of stem cells in cartilage tissue engineering. Biomedicine & Pharmacotherapy 131, 110652 (2020).
  Medline CASGoogle Scholar
• 124. Wang J, Wang Y, Sun X et al. Biomimetic cartilage scaffold with orientated porous structure of two factors for cartilage repair of knee osteoarthritis. Artificial Cells, Nanomedicine, and Biotechnology 47(1), 1710–1721 (2019).
  Medline CASGoogle Scholar
• 125. Johnson K, Zhu S, Tremblay MS et al. A stem cell-based approach to cartilage repair. Science 336(6082), 717–721 (2012).
  Medline CASGoogle Scholar
• 126. Hayek A, Kerstetter-Fogle AE, Sachlos E, Bollenbach T. Kartogenin: a game-changer in regenerative medicine. Regenerative Medicine 7(4), 475 (2012).
  Google Scholar
• 127. Yano F, Ohba S, Hosaka Y, Saito T, Chung U-I. Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model. Ann. Rheum. Dis. 73(11), 2062–2064 (2014).
  MedlineGoogle Scholar
• 128. Yano F, Hojo H, Ohba S et al. A novel disease-modifying osteoarthritis drug candidate targeting Runx1. Ann. Rheum. Dis. 72(5), 748–753 (2013).
  Medline CASGoogle Scholar
• 129. Chen Y, Sun H, Yao X et al. Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs. Cell. Mol. Life Sci. 78(24), 8127–8155 (2021).
  Medline CASGoogle Scholar
• 130. Choi E, Lee J, Lee S et al. Potential therapeutic application of small molecule with sulfonamide for chondrogenic differentiation and articular cartilage repair. Bioorganic & Medicinal Chemistry Letters 26(20), 5098–5102 (2016).
  Medline CASGoogle Scholar
• 131. Heck BE, Park JJ, Makani V, Kim E-C, Kim DH. PPAR-δ agonist with mesenchymal stem cells induces type II collagen-producing chondrocytes in human arthritic synovial fluid. Cell Transplant. 26(8), 1405–1417 (2017).
  MedlineGoogle Scholar