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Cartilage repair using stem cells & biomaterials: advancement from bench to bedside

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Abstract

Osteoarthritis (OA) involves gradual destruction of articular cartilagemanifested by pain, stiffness of joints, and impaired movement especially in knees and hips. Non-vascularity of this tissue hinders its self-regenerative capacity and thus, the application of reparative or restorative modalities becomes imperative in OA treatment. In recent years, stem cell-based therapies have been explored as potential modalities for addressing OA complications. While mesenchymal stem cells (MSCs) hold immense promise, the recapitulation of native articular cartilage usingMSCs remains elusive. In this review, we have highlighted the chondrogenic potential of MSCs, factors guiding in vitro chondrogenic differentiation, biomaterials available for cartilage repair, their current market status, and the outcomes of major clinical trials. Our search on ClinicalTrials.gov using terms “stem cell” and “osteoarthritis” yielded 83 results. An analysis of the 29 trials that have been completed revealed differences in source of MSCs (bone marrow, adipose tissue, umbilical cord etc.), cell type (autologous or allogenic), and dose administered. Moreover, only 02 out of 29 studies have reported the use of matrix for cartilage repair. From future perspective, aconsensus on choice of cells, differentiation inducers, biomaterials, and clinical settings might pave a way for concocting robust strategies to improve the clinical applicability of biomimetic neocartilage constructs.

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References

  1. Hayami T, Pickarski M, Zhuo Y, Wesolowski GA, Rodan GA, Duong LT (2006) Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 38(2):234–243

    PubMed  Google Scholar 

  2. Kaur R, Ghosh A, Singh A (2018) Prevalence of knee osteoarthritis and its determinants in 30–60 years old women of Gurdaspur, Punjab. Int J Med Sci Public Health 7(10):825–831

    Google Scholar 

  3. Parkinson L, Moorin R, Peeters G, Byles J, Blyth F, Caughey G, Cunich M, Magin P, March L, Pond D (2016) Incident osteoarthritis associated with increased allied health services use in ‘baby boomer’ Australian women. Aust NZ J Public Health 40:356–361

    Google Scholar 

  4. Pal CP, Singh P, Chaturvedi S, Pruthi KK, Vij A (2016) Epidemiology of knee osteoarthritis in India and related factors. Indian J Orthop 50(5):518

    PubMed  PubMed Central  Google Scholar 

  5. Azad CS, Singh AK, Poorti Pandey P, Singh M, Chaudhary P, Tia N, Rastogi A, Gambhir IS (2017) Osteoarthritis in India: an epidemiologic aspect. Int J Recent Sci Res 8(10):20918–20922

    Google Scholar 

  6. Zhang Y, Jordan JM (2010) Epidemiology of osteoarthritis. Clin Geriatr Med 26(3):355–369

    PubMed  PubMed Central  Google Scholar 

  7. Symmons D, Turner G, Webb R, Asten P, Barrett E, Lunt M, Scott D, Silman A (2002) The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology 41(7):793–800

    CAS  PubMed  Google Scholar 

  8. Roseti L, Desando G, Cavallo C, Petretta M, Grigolo B (2019) Articular cartilage regeneration in osteoarthritis. Cells 8(11):1305

    CAS  PubMed Central  Google Scholar 

  9. Nakamura A, Kapoor M (2016) mTOR: a critical mediator of articular cartilage homeostasis. Molecules to medicine with mTOR. Elsevier, Amsterdam, pp 57–68

    Google Scholar 

  10. Jeng L, Kwong FN, Spector M (2011) Chapter 42—articular cartilage. In: Atala A, Lanza R, Thomson JA, Nerem R (eds) Principles of regenerative medicine, 2nd edn. Academic Press, San Diego, pp 761–777. https://doi.org/10.1016/B978-0-12-381422-7.10042-2

    Chapter  Google Scholar 

  11. Reinold MM, Macrina LC, Ostrander RV, CainEL DJR (2006) Rehabilitation after articular cartilage repair procedures: osteochondral autograft transplantation and autologous chondrocyte implantation. Postsurgical orthopedic sports rehabilitation knee and shoulder. Elsevier, Saint Louis, pp 383–407

    Google Scholar 

  12. Fisher M, Ackley T, Richard K, Oei B, Dealy CN (2019) Osteoarthritis at the cellular level: mechanisms, clinical perspectives, and insights from development. Reference module in biomedical sciences encyclopedia of biomedical engineering. Elsevier, Amsterdam, pp 660–676

    Google Scholar 

  13. Dubey NK, Mishra VK, Dubey R, Syed-Abdul S, Wang JR, Wang PD, Deng W-P (2018) Combating osteoarthritis through stem cell therapies by rejuvenating cartilage: a review. Stem Cells Int. https://doi.org/10.1155/2018/5421019

    Article  PubMed  PubMed Central  Google Scholar 

  14. Maumus M, Pers Y-M, Ruiz M, Jorgensen C, Noël D (2018) Mesenchymal stem cells and regenerative medicine: future perspectives in osteoarthritis. Med Sci (Paris) 34(12):1092–1099. https://doi.org/10.1051/medsci/2018294

    Article  Google Scholar 

  15. Vina ER, Kwoh CK (2018) Epidemiology of osteoarthritis: literature update. Curr Opin Rheumatol 30(2):160

    PubMed  PubMed Central  Google Scholar 

  16. Cole BJ, Pascual-Garrido C, Grumet RC (2009) Surgical management of articular cartilage defects in the knee. JBJS 91(7):1778–1790

    Google Scholar 

  17. Bhatia S, Hsu A, Lin EC, Chalmers P, Ellman M, Cole BJ, Verma NN (2012) Surgical treatment options for the young and active middle-aged patient with glenohumeral arthritis. Adv Orthop. https://doi.org/10.1155/2012/846843

    Article  PubMed  PubMed Central  Google Scholar 

  18. McGowan KB, Stiegman G (2013) Regulatory challenges for cartilage repair technologies. Cartilage 4(1):4–11

    PubMed  PubMed Central  Google Scholar 

  19. Browne JE, Branch TP (2000) Surgical alternatives for treatment of articular cartilage lesions. J Am Acad Orthop Surg 8(3):180–189

    CAS  PubMed  Google Scholar 

  20. Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19(5):477–484

    PubMed  Google Scholar 

  21. Niemeyer P, Albrecht D, Andereya S, Angele P, Ateschrang A, Aurich M, Baumann M, Bosch U, Erggelet C, Fickert S (2016) Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group “Clinical Tissue Regeneration” of the German Society of Orthopaedics and Trauma (DGOU). Knee 23(3):426–435

    CAS  PubMed  Google Scholar 

  22. Zhang Z, Zhong X, Ji H, Tang Z, Bai J, Yao M, Hou J, Zheng M, Wood DJ, Sun J (2014) Matrix-induced autologous chondrocyte implantation for the treatment of chondral defects of the knees in Chinese patients. Drug Des Dev Ther 8:2439

    Google Scholar 

  23. Mandelbaum B, Browne JE, Fu F, Micheli LJ, Moseley JB, Erggelet C, Anderson AF (2007) Treatment outcomes of autologous chondrocyte implantation for full-thickness articular cartilage defects of the trochlea. Am J Sports Med 35(6):915–921

    PubMed  Google Scholar 

  24. Brittberg M (2009) Cell carriers as the next generation of cell therapy for cartilage repair: a review of the matrix-induced autologous chondrocyte implantaion procedure. Am J Sports Med 38(6):1259–1271

    PubMed  Google Scholar 

  25. Guzzo RM, Gibson J, Xu RH, Lee FY, Drissi H (2013) Efficient differentiation of human iPSC-derived mesenchymal stem cells to chondroprogenitor cells. J Cell Biochem 114(2):480–490

    CAS  PubMed  Google Scholar 

  26. Ohnuki M, Takahashi K (2015) Present and future challenges of induced pluripotent stem cells. Philos Trans R Soc B 370(1680):20140367

    Google Scholar 

  27. Lund RJ, Närvä E, Lahesmaa R (2012) Genetic and epigenetic stability of human pluripotent stem cells. Nat Rev Genet 13(10):732

    CAS  PubMed  Google Scholar 

  28. Zhang R, Ma J, Han J, Zhang W, Ma J (2019) Mesenchymal stem cell related therapies for cartilage lesions and osteoarthritis. Am J Transl Res 11(10):6275

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084

    CAS  PubMed  Google Scholar 

  30. Yi T, Song SU (2012) Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharmacal Res 35(2):213–221

    CAS  Google Scholar 

  31. Frieedenstein A, Petrakova K, Kurolesova A, Frolova G (1968) Hetrotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoetic tissue. Transplantacion 6(2):230

    Google Scholar 

  32. Pelttari K, Winter A, Steck E, Goetzke K, Hennig T, Ochs BG, Aigner T, Richter W (2006) Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54(10):3254–3266

    CAS  PubMed  Google Scholar 

  33. Wang W, Li B, Yang J, Xin L, Li Y, Yin H, Qi Y, Jiang Y, Ouyang H, Gao C (2010) The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs. Biomaterials 31(34):8964–8973

    CAS  PubMed  Google Scholar 

  34. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317

    CAS  PubMed  Google Scholar 

  35. Kohli N, Al-Delfi IR, Snow M, Sakamoto T, Miyazaki T, Nakajima H, Uchida K, Johnson WE (2019) CD271-selected mesenchymal stem cells from adipose tissue enhance cartilage repair and are less angiogenic than plastic adherent mesenchymal stem cells. Sci Rep 9(1):3194

    PubMed  PubMed Central  Google Scholar 

  36. Mak J, Jablonski C, Leonard C, Dunn JF, Raharjo E, Matyas J, Biernaskie J, Krawetz R (2016) Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model. Sci Rep 6:23076

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Neumann K, Dehne T, Endres M, Erggelet C, Kaps C, Ringe J, Sittinger M (2008) Chondrogenic differentiation capacity of human mesenchymal progenitor cells derived from subchondral cortico-spongious bone. J Orthop Res 26(11):1449–1456

    CAS  PubMed  Google Scholar 

  38. Johnstone B, Hering TM, Caplan AL, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272

    CAS  PubMed  Google Scholar 

  39. Berebichez-Fridman R, Montero-Olvera PR (2018) Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J 18(3):e264–e277. https://doi.org/10.18295/squmj.2018.18.03.002

    Article  PubMed  PubMed Central  Google Scholar 

  40. Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H, Weber RM, Ewerbeck V, Richter W (2003) Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow–derived and adipose tissue–derived stromal cells. Arthritis Rheum 48(2):418–429

    CAS  PubMed  Google Scholar 

  41. Rodbell M (1966) Metabolism of isolated fat cells II. The similar effects of phospholipase C (Clostridium perfringens α toxin) and of insulin on glucose and amino acid metabolism. J Biol Chem 241(1):130–139

    CAS  PubMed  Google Scholar 

  42. Priya N, Sarcar S, Majumdar AS, SundarRaj S (2014) Explant culture: a simple, reproducible, efficient and economic technique for isolation of mesenchymal stromal cells from human adipose tissue and lipoaspirate. J Tissue Eng Regen Med 8(9):706–716

    CAS  PubMed  Google Scholar 

  43. Hatakeyama A, Uchida S, Utsunomiya H, Tsukamoto M, Nakashima H, Nakamura E, Pascual-Garrido C, Sekiya I, Sakai A (2017) Isolation and characterization of synovial mesenchymal stem cell derived from hip joints: a comparative analysis with a matched control knee group. Stem Cells Int. https://doi.org/10.1155/2017/9312329

    Article  PubMed  PubMed Central  Google Scholar 

  44. Im G-I, Shin Y-W, Lee K-B (2005) Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells? Osteoarthritis Cartilage 13(10):845–853

    PubMed  Google Scholar 

  45. Koga H, Muneta T, Nagase T, Nimura A, Ju Y, Mochizuki T, Sekiya I (2008) Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res. 333(2):207–215. https://doi.org/10.1007/s00441-008-0633-5

    Article  PubMed  Google Scholar 

  46. Roobrouck VD, Ulloa-Montoya F, Verfaillie CM (2008) Self-renewal and differentiation capacity of young and aged stem cells. Exp Cell Res 314(9):1937–1944

    CAS  PubMed  Google Scholar 

  47. Ramezanifard R, Kabiri M, Ahvaz HH (2017) Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses. EXCLI J 16:1031

    PubMed  PubMed Central  Google Scholar 

  48. Hassan G, Bahjat M, Kasem I, Soukkarieh C, Aljamali M (2018) Platelet lysate induces chondrogenic differentiation of umbilical cord-derived mesenchymal stem cells. Cell Mol Biol Lett 23(1):11

    PubMed  PubMed Central  Google Scholar 

  49. Boeuf S, Steck E, Pelttari K, Hennig T, Buneß A, Benz K, Witte D, Sültmann H, Poustka A, Richter W (2008) Subtractive gene expression profiling of articular cartilage and mesenchymal stem cells: serpins as cartilage-relevant differentiation markers. Osteoarthritis Cartilage 16(1):48–60

    CAS  PubMed  Google Scholar 

  50. Shimaya M, Muneta T, Ichinose S, Tsuji K, Sekiya I (2010) Magnesium enhances adherence and cartilage formation of synovial mesenchymal stem cells through integrins. Osteoarthritis Cartilage 18(10):1300–1309

    CAS  PubMed  Google Scholar 

  51. Farrell E, Both SK, Odörfer KI, Koevoet W, Kops N, O'Brien FJ, De Jong RJB, Verhaar JA, Cuijpers V, Jansen J (2011) In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells. BMC Musculoskelet Disord 12(1):31

    PubMed  PubMed Central  Google Scholar 

  52. Hamid AA, Idrus RBH, Saim AB, Sathappan S, Chua K-H (2012) Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation. Clinics 67(2):099–106

    Google Scholar 

  53. Lee HH, O'Malley MJ, Friel NA, Chu CR (2013) Effects of doxycycline on mesenchymal stem cell chondrogenesis and cartilage repair. Osteoarthritis Cartilage 21(2):385–393

    CAS  PubMed  Google Scholar 

  54. Murphy MK, Huey DJ, Hu JC, Athanasiou KA (2015) TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells. Stem Cells 33(3):762–773

    CAS  PubMed  Google Scholar 

  55. Nakagawa Y, Muneta T, Otabe K, Ozeki N, Mizuno M, Udo M, Saito R, Yanagisawa K, Ichinose S, Koga H (2016) Cartilage derived from bone marrow mesenchymal stem cells expresses lubricin in vitro and in vivo. PLoS ONE 11(2):e0148777

    PubMed  PubMed Central  Google Scholar 

  56. Ogata Y, Mabuchi Y, Yoshida M, Suto EG, Suzuki N, Muneta T, Sekiya I, Akazawa C (2015) Purified human synovium mesenchymal stem cells as a good resource for cartilage regeneration. PLoS ONE 10(6):e0129096

    PubMed  PubMed Central  Google Scholar 

  57. Xu F-T, Li H-M, Zhao C-Y, Liang Z-J, Huang M-H, Li Q, Chen Y-C, Chi G-Y (2015) Characterization of chondrogenic gene expression and cartilage phenotype differentiation in human breast adipose-derived stem cells promoted by ginsenoside Rg1 in vitro. Cell Physiol Biochem 37(5):1890–1902

    CAS  PubMed  Google Scholar 

  58. Yoo JU, Barthel TS, Nishimura K, Solchaga L, Caplan AI, Goldberg VM, Johnstone B (1998) The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells. JBJS 80(12):1745–1757

    CAS  Google Scholar 

  59. Hu T, Xu H, Wang C, Qin H, An Z (2018) Magnesium enhances the chondrogenic differentiation of mesenchymal stem cells by inhibiting activated macrophage-induced inflammation. Sci Rep 8(1):1–13

    Google Scholar 

  60. Sorrell JM, Somoza RA, Caplan AI (2018) Human mesenchymal stem cells induced to differentiate as chondrocytes follow a biphasic pattern of extracellular matrix production. J Orthop Res 36(6):1757–1766

    CAS  PubMed  Google Scholar 

  61. Huang X, Zhong L, Hendriks J, Post J, Karperien M (2018) The effects of the WNT-signaling modulators BIO and PKF118-310 on the chondrogenic differentiation of human mesenchymal stem cells. Int J Mol Sci 19(2):561

    PubMed Central  Google Scholar 

  62. Al-Yamani A, Kalamegam G, Ahmed F, Abbas M, Sait KHW, Anfinan N, Al-Wasiyah MK, Huwait EA, Gari M, Al-Qahtani M (2018) Evaluation of in vitro chondrocytic differentiation: a stem cell research initiative at the King Abdulaziz University, Kingdom of Saudi Arabia. Bioinformation 14(2):53

    PubMed  PubMed Central  Google Scholar 

  63. Mason JM, Grande DA, Barcia M, Grant R, Pergolizzi RG, Breitbart AS (1998) Expression of human bone morphogenic protein 7 in primary rabbit perisoteal cells: potential utility in gene therapy for osteochondral repair. Gene Ther 5:1098–1104

    CAS  PubMed  Google Scholar 

  64. Steinert AF, Palmer GD, Pilapil C, Nöth U, Evans CH, Ghivizzani SC (2008) Enhanced in vitro chondrogenesis of primary mesenchymal stem cells by combined gene transfer. Tissue Eng A 15(5):1127–1139

    Google Scholar 

  65. Steinert AF, Proffen B, Kunz M, Hendrich C, Ghivizzani SC, Nöth U, Rethwilm A, Eulert J, Evans CH (2009) Hypertrophy is induced during the in vitro chondrogenic differentiation of human mesenchymal stem cells by bone morphogenetic protein-2 and bone morphogenetic protein-4 gene transfer. Arthritis Res Ther 11(5):R148

    PubMed  PubMed Central  Google Scholar 

  66. Gelse K, von der Mark K, Aigner T, Park J, Schneider H (2003) Articular cartilage repair by gene therapy using growth factor–producing mesenchymal cells. Arthritis Rheum 48(2):430–441

    CAS  PubMed  Google Scholar 

  67. Palmer GD, Steinert A, Pascher A, Gouze E, Gouze J-N, Betz O, Johnstone B, Evans CH, Ghivizzani SC (2005) Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro. Mol Ther 12(2):219–228

    CAS  PubMed  Google Scholar 

  68. Portron S, Hivernaud V, Merceron C, Lesoeur J, Masson M, Gauthier O, Vinatier C, Beck L, Guicheux J (2015) Inverse regulation of early and late chondrogenic differentiation by oxygen tension provides cues for stem cell-based cartilage tissue engineering. Cell Physiol Biochem 35(3):841–857

    CAS  PubMed  Google Scholar 

  69. Taheem DK, Foyt DA, Loaiza S, Ferreira SA, Ilic D, Auner HW, Grigoriadis AE, Jell G, Gentleman E (2018) Differential regulation of human bone marrow mesenchymal stromal cell chondrogenesis by hypoxia inducible factor-1α hydroxylase inhibitors. Stem Cells 36(9):1380–1392

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Gómez-Leduc T, Desancé M, Hervieu M, Legendre F, Ollitrault D, de Vienne C, Herlicoviez M, Galéra P, Demoor M (2017) Hypoxia is a critical parameter for chondrogenic differentiation of human umbilical cord blood mesenchymal stem cells in type I/III collagen sponges. Int J Mol Sci 18(9):1933

    PubMed Central  Google Scholar 

  71. Fan J, Varshney RR, Ren L, Cai D, Wang D-A (2009) Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration. Tissue Eng B 15(1):75–86

    CAS  Google Scholar 

  72. Tamaddon M, Burrows M, Ferreira S, Dazzi F, Apperley J, Bradshaw A, Brand D, Czernuszka J, Gentleman E (2017) Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro. Sci Rep 7:43519

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Schätti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, Stoddart M (2011) A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur Cell Mater 22(214–225):b97

    Google Scholar 

  74. Cochis A, Grad S, Stoddart M, Fare S, Altomare L, Azzimonti B, Alini M, Rimondini L (2017) Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel. Sci Rep 7:45018

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Cao W, Lin W, Cai H, Chen Y, Man Y, Liang J, Wang Q, Sun Y, Fan Y, Zhang X (2019) Dynamic mechanical loading facilitated chondrogenic differentiation of rabbit BMSCs in collagen scaffolds. Regen Biomater 6(2):99–106

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Cooke M, Allon A, Cheng T, Kuo A, Kim H, Vail T, Marcucio R, Schneider R, Lotz J, Alliston T (2011) Structured three-dimensional co-culture of mesenchymal stem cells with chondrocytes promotes chondrogenic differentiation without hypertrophy. Osteoarthritis Cartilage 19(10):1210–1218

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Pleumeekers MM, Nimeskern L, Koevoet J, Karperien M, Stok KS, van Osch GJ (2018) Trophic effects of adipose-tissue-derived and bone-marrow-derived mesenchymal stem cells enhance cartilage generation by chondrocytes in co-culture. PLoS ONE 13(2):e0190744

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Wang H, Yan X, Jiang Y, Wang Z, Li Y, Shao Q (2018) The human umbilical cord stem cells improve the viability of OA degenerated chondrocytes. Mol Med Rep 17(3):4474–4482

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Li X, Duan L, Liang Y, Zhu W, Xiong J, Wang D (2016) Human umbilical cord blood-derived mesenchymal stem cells contribute to chondrogenesis in coculture with chondrocytes. Biomed Res Int. https://doi.org/10.1155/2016/3827057

    Article  PubMed  PubMed Central  Google Scholar 

  80. Cao Z, Dou C, Dong S (2014) Scaffolding biomaterials for cartilage regeneration. J Nanomater 2014:4

    Google Scholar 

  81. Armiento A, Stoddart M, Alini M, Eglin D (2018) Biomaterials for articular cartilage tissue engineering: learning from biology. Acta Biomater 65:1–20

    CAS  PubMed  Google Scholar 

  82. Lam AT, Reuveny S, Oh SK-W (2020) Human mesenchymal stem cell therapy for cartilage repair: review on isolation, expansion, and constructs. Stem Cell Res 44:101738

    CAS  PubMed  Google Scholar 

  83. Rai V, Dilisio MF, Dietz NE, Agrawal DK (2017) Recent strategies in cartilage repair: a systemic review of the scaffold development and tissue engineering. J Biomed Mater Res A 105(8):2343–2354

    CAS  PubMed  Google Scholar 

  84. Estes BT, Wu AW, Guilak F (2006) Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6. Arthritis Rheum 54(4):1222–1232

    CAS  PubMed  Google Scholar 

  85. Kafienah W, Mistry S, Perry MJ, Politopoulou G, Hollander AP (2007) Pharmacological regulation of adult stem cells: chondrogenesis can be induced using a synthetic inhibitor of the retinoic acid receptor. Stem Cells 25(10):2460–2468

    CAS  PubMed  Google Scholar 

  86. Xu J, Wang W, Ludeman M, Cheng K, Hayami T, Lotz JC, Kapila S (2008) Chondrogenic differentiation of human mesenchymal stem cells in three-dimensional alginate gels. Tissue Eng A 14(5):667–680

    CAS  Google Scholar 

  87. Kurth T, Hedbom E, Shintani N, Sugimoto M, Chen F, Haspl M, Martinovic S, Hunziker EB (2007) Chondrogenic potential of human synovial mesenchymal stem cells in alginate. Osteoarthritis Cartilage 15(10):1178–1189

    CAS  PubMed  Google Scholar 

  88. Yang Z, Wu Y, Li C, Zhang T, Zou Y, Hui JH, Ge Z, Lee EH (2011) Improved mesenchymal stem cells attachment and in vitro cartilage tissue formation on chitosan-modified poly (l-lactide-co-epsilon-caprolactone) scaffold. Tissue Eng A 18(3–4):242–251

    CAS  Google Scholar 

  89. Wu J, Xue K, Li H, Sun J, Liu K (2013) Improvement of PHBV scaffolds with bioglass for cartilage tissue engineering. PLoS ONE 8(8):e71563

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Kim J, Lin B, Kim S, Choi B, Evseenko D, Lee M (2015) TGF-β1 conjugated chitosan collagen hydrogels induce chondrogenic differentiation of human synovium-derived stem cells. J Biol Eng 9(1):1

    PubMed  PubMed Central  Google Scholar 

  91. Focaroli S, Teti G, Salvatore V, Orienti I, Falconi M (2016) Calcium/cobalt alginate beads as functional scaffolds for cartilage tissue engineering. Stem Cells Int. https://doi.org/10.1155/2016/2030478

    Article  PubMed  PubMed Central  Google Scholar 

  92. Xiao T, Guo W, Chen M, Hao C, Gao S, Huang J, Yuan Z, Zhang Y, Wang M, Li P (2017) Fabrication and in vitro study of tissue-engineered cartilage scaffold derived from Wharton’s jelly extracellular matrix. Biomed Res Int. https://doi.org/10.1155/2017/5839071

    Article  PubMed  PubMed Central  Google Scholar 

  93. Wise JK, Yarin AL, Megaridis CM, Cho M (2009) Chondrogenic differentiation of human mesenchymal stem cells on oriented nanofibrous scaffolds: engineering the superficial zone of articular cartilage. Tissue Eng A 15(4):913–921

    CAS  Google Scholar 

  94. Galeano-Garces C, Camilleri ET, Riester SM, Dudakovic A, Larson DR, Qu W, Smith J, Dietz AB, Im H-J, Krych AJ (2017) Molecular validation of chondrogenic differentiation and hypoxia responsiveness of platelet-lysate expanded adipose tissue-derived human mesenchymal stromal cells. Cartilage 8(3):283–299

    CAS  PubMed  Google Scholar 

  95. Shie M-Y, Chang W-C, Wei L-J, Huang Y-H, Chen C-H, Shih C-T, Chen Y-W, Shen Y-F (2017) 3D printing of cytocompatible water-based light-cured polyurethane with hyaluronic acid for cartilage tissue engineering applications. Materials 10(2):136

    PubMed Central  Google Scholar 

  96. Huang S, Song X, Li T, Xiao J, Chen Y, Gong X, Zeng W, Yang L, Chen C (2017) Pellet coculture of osteoarthritic chondrocytes and infrapatellar fat pad-derived mesenchymal stem cells with chitosan/hyaluronic acid nanoparticles promotes chondrogenic differentiation. Stem Cell Res Ther 8(1):264

    PubMed  PubMed Central  Google Scholar 

  97. Calabrese G, Forte S, Gulino R, Cefalì F, Figallo E, Salvatorelli L, Maniscalchi ET, Angelico G, Parenti R, Gulisano M (2017) Combination of collagen-based scaffold and bioactive factors induces adipose-derived mesenchymal stem cells chondrogenic differentiation in vitro. Front Physiol 8:50

    PubMed  PubMed Central  Google Scholar 

  98. Sanjurjo-Rodríguez C, Castro-Viñuelas R, Hermida-Gómez T, Fuentes-Boquete IM, de Toro FJ, Blanco FJ, Díaz-Prado SM (2017) Human cartilage engineering in an in vitro repair model using collagen scaffolds and mesenchymal stromal cells. Int J Med Sci 14(12):1257

    PubMed  PubMed Central  Google Scholar 

  99. Barlian A, Judawisastra H, Alfarafisa NM, Wibowo UA, Rosadi I (2018) Chondrogenic differentiation of adipose-derived mesenchymal stem cells induced by l-ascorbic acid and platelet rich plasma on silk fibroin scaffold. PeerJ 6:e5809

    PubMed  PubMed Central  Google Scholar 

  100. https://www.matricel.net/en/products.html.hwmneph

  101. https://www.orthocell.com.au/cartilage-regeneration

  102. https://www.osiris.com/cartiform/

  103. Huang H, Xu H, Zhang J (2019) Current tissue engineering approaches for cartilage regeneration. https://doi.org/10.5772/intechopen.84429

  104. https://www.arthro-kinetics.com/page-4

  105. https://fintel.io/doc/sec-hsgx-histogenics-10k-annual-report-2019-march-21-17977

  106. https://www.aesculapbiologics.com/en/patients/novocart-3d.html

  107. https://www.ema.europa.eu/en/medicines/human/withdrawn-applications/hyalograft-c-autog

  108. https://www.smith-nephew.com/professional/products/all-products/mosaicplasty/

  109. https://www.cellcotec.com/www.cellcotec.com/technology.phppage28/

  110. Harrison L (2015) Chondrocyte therapy effective in knee cartilage repair. https://www.medscape.com/viewarticle/842043

  111. BROOKS A Me and my operation: cartilage transplant. https://www.dailymail.co.uk/health/article-76501/Me-operation-cartilage-transplant.html

  112. Bapat S, Hubbard D, Munjal A, Hunter M, Fulzele S (2018) Pros and cons of mouse models for studying osteoarthritis. Clin Transl Med 7(1):36

    PubMed  PubMed Central  Google Scholar 

  113. Kuyinu EL, Narayanan G, Nair LS, Laurencin CT (2016) Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res 11(1):19

    PubMed  PubMed Central  Google Scholar 

  114. Van den Borne M, Raijmakers N, Vanlauwe J, Victor J, De Jong S, Bellemans J, Saris D (2007) International Cartilage Repair Society (ICRS) and Oswestry macroscopic cartilage evaluation scores validated for use in Autologous Chondrocyte Implantation (ACI) and microfracture. Osteoarthritis Cartilage 15(12):1397–1402

    PubMed  Google Scholar 

  115. Lee W, Maeng G, Jeon R, Rho G, Lee S (2011) 210 comparative characterization of mesenchymal stem cells derived from miniature pig synovium, synovial fluid and bone marrow. Reprod Fertil Dev 24(1):217–217

    Google Scholar 

  116. Prado AAF, Favaron PO, da Silva LCLC, Baccarin RYA, Miglino MA, Maria DA (2015) Characterization of mesenchymal stem cells derived from the equine synovial fluid and membrane. BMC Vet Res 11(1):281

    PubMed  PubMed Central  Google Scholar 

  117. Zayed M, Caniglia C, Misk N, Dhar MS (2017) Donor-matched comparison of chondrogenic potential of equine bone marrow-and synovial fluid-derived mesenchymal stem cells: implications for cartilage tissue regeneration. Front Vet Sci 3:121

    PubMed  PubMed Central  Google Scholar 

  118. Fernandes TL, Shimomura K, Asperti A, Pinheiro CCG, Caetano HVA, Oliveira CRG, Nakamura N, Hernandez AJ, Bueno DF (2018) Development of a novel large animal model to evaluate human dental pulp stem cells for articular cartilage treatment. Stem Cell Rev Rep 14(5):734–743

    CAS  PubMed  Google Scholar 

  119. Meng F, Zhang Z, Huang G, Chen W, Zhang Z, He A, Liao W (2016) Chondrogenesis of mesenchymal stem cells in a novel hyaluronate-collagen-tricalcium phosphate scaffolds for knee repair. Eur Cell Mater 31:79–94

    CAS  PubMed  Google Scholar 

  120. Hermeto L, DeRossi R, Oliveira R, Pesarini J, Antoniolli-Silva A, Jardim P, Santana A, Deffune E, Rinaldi J, Justulin L (2016) Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis. Genet Mol Res 15(3):gmr-15038569

    Google Scholar 

  121. Kohli N, Al-Delfi IR, Snow M, Sakamoto T, Miyazaki T, Nakajima H, Uchida K, Johnson WE (2019) CD271-selected mesenchymal stem cells from adipose tissue enhance cartilage repair and are less angiogenic than plastic adherent mesenchymal stem cells. Sci Rep 9(1):1–12

    Google Scholar 

  122. Prasadam I, Akuien A, Friis TE, Fang W, Mao X, Crawford RW, Xiao Y (2018) Mixed cell therapy of bone marrow-derived mesenchymal stem cells and articular cartilage chondrocytes ameliorates osteoarthritis development. Lab Invest 98(1):106–116

    CAS  PubMed  Google Scholar 

  123. Knuth CA, Kiernan CH, Palomares Cabeza V, Lehmann J, Witte-Bouma J, ten Berge D, Brama PA, Wolvius EB, Strabbing EM, Koudstaal MJ (2018) Isolating pediatric mesenchymal stem cells with enhanced expansion and differentiation capabilities. Tissue Eng C 24(6):313–321

    CAS  Google Scholar 

  124. Daly AC, Freeman FE, Gonzalez-Fernandez T, Critchley SE, Nulty J, Kelly DJ (2017) 3D bioprinting for cartilage and osteochondral tissue engineering. Adv Healthc Mater 6(22):1700298

    Google Scholar 

  125. Wang Y, Yu D, Liu Z, Zhou F, Dai J, Wu B, Zhou J, Heng BC, Zou XH, Ouyang H (2017) Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther 8(1):189

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Mianehsaz E, Mirzaei HR, Mahjoubin-Tehran M, Rezaee A, Sahebnasagh R, Pourhanifeh MH, Mirzaei H, Hamblin MR (2019) Mesenchymal stem cell-derived exosomes: a new therapeutic approach to osteoarthritis? Stem Cell Res Ther 10(1):340

    PubMed  PubMed Central  Google Scholar 

  127. Miyaki S, Lotz MK (2018) Extracellular vesicles in cartilage homeostasis and osteoarthritis. Curr Opin Rheumatol 30(1):129

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Liu X, Yang Y, Li Y, Niu X, Zhao B, Wang Y, Bao C, Xie Z, Lin Q, Zhu L (2017) Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale 9(13):4430–4438

    CAS  PubMed  Google Scholar 

  129. Mobasheri A (2019) Future cell and gene therapy for osteoarthritis (OA): potential for using mammalian protein production platforms, irradiated and transfected protein packaging cell lines for over-production of therapeutic proteins and growth factors. Cell Biol Transl Med 8:17–31

    Google Scholar 

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Acknowledgements

The authors gratefully acknowledge DattMediproducts Pvt. Ltd. for supporting the work and providing the space for research work. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. Department of Life Science (R & D), Datt Mediproducts Pvt. Ltd., Roz Ka Meo Industrial Area, Nuh, District Mewat, Haryana, 122103, India

    Anupama Kakkar, Aarti Singh, Sumit Kumar Saraswat, Supriya Srivastava, Nitin Khatri, Rakesh Kumar Nagar, Mukesh Kumar, Poonam Meena, Rajan Datt & Siddharth Pandey

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  1. Anupama Kakkar
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Kakkar, A., Singh, A., Saraswat, S.K. et al. Cartilage repair using stem cells & biomaterials: advancement from bench to bedside. Mol Biol Rep 47, 8007–8021 (2020). https://doi.org/10.1007/s11033-020-05748-1

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