Login Register Cart 0
Generic placeholder image

Current Reviews in Clinical and Experimental Pharmacology

Editor-in-Chief

ISSN (Print): 2772-4328
ISSN (Online): 2772-4336

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Review Article

Advanced Therapeutic Medicinal Products in Bone and Cartilage Defects

Author(s): Dylana Diaz-Solano, Bahareh Sadri, Maria Peshkova, Anastasia Shpichka, Olga Smirnova, Roshanak Shams*, Peter Timashev* and Massoud Vosough*

Volume 19, Issue 4, 2024

Published on: 24 January, 2024

Page: [355 - 369] Pages: 15

DOI: 10.2174/0127724328274436231207062008

Price: $65

conference banner
Abstract

The number of patients with functional loss of bone and cartilage tissue has shown an increasing trend. Insufficient or inappropriate conventional treatments applied for trauma, orthopedic diseases, or other bone and cartilage-related disorders can lead to bone and cartilage damage. This represents a worldwide public health issue and a significant economic burden. Advanced therapeutic medicinal products (ATMPs) proposed promising alternative therapeutic modalities by application of cell-based and tissue engineering approaches. Recently, several ATMPs have been developed to promote bone and cartilage tissue regeneration. Fifteen ATMPs, two related to bone and 13 related to cartilage, have received regulatory approval and marketing authorization. However, four ATMPs were withdrawn from the market for various reasons. However, ATMPs that are still on the market have demonstrated positive results, their broad application faced limitations. The development and standardization of methodologies will be a major challenge in the coming decades. Currently, the number of ATMPs in clinical trials using mesenchymal stromal cells or chondrocytes indicates a growing recognition that current ATMPs can be improved. Research on bone and cartilage tissue regeneration continues to expand. Cell-based therapies are likely to be clinically supported by the new ATMPs, innovative fabrication processes, and enhanced surgical approaches. In this study, we highlighted the available ATMPs that have been used in bone and cartilage defects and discussed their advantages and disadvantages in clinical applications.

Keywords: ATMPs in bone disorders, bone regeneration, cartilage regeneration, regenerative medicine, mesenchymal stromal cell, cell-based therapy.

« Previous Next »
Graphical Abstract

[1]
Borgström F, Karlsson L, Ortsäter G, et al. Fragility fractures in Europe: Burden, management and opportunities. Arch Osteoporos 2020; 15(1): 59.
[http://dx.doi.org/10.1007/s11657-020-0706-y] [PMID: 32306163]
[2]
Tatangelo G, Watts J, Lim K, et al. The cost of osteoporosis, osteopenia, and associated fractures in Australia in 2017: Cost of osteoporosis, osteopenia, and fractures. J Bone Miner Res 2019; 34(4): 616-25.
[http://dx.doi.org/10.1002/jbmr.3640] [PMID: 30615801]
[3]
Williamson S, Landeiro F, McConnell T, et al. Costs of fragility hip fractures globally: A systematic review and meta-regression analysis. Osteoporos Int 2017; 28(10): 2791-800.
[http://dx.doi.org/10.1007/s00198-017-4153-6] [PMID: 28748387]
[4]
Polinder S, Haagsma J, Panneman M, Scholten A, Brugmans M, Van Beeck E. The economic burden of injury: Health care and productivity costs of injuries in the Netherlands. Accid Anal Prev 2016; 93: 92-100.
[http://dx.doi.org/10.1016/j.aap.2016.04.003] [PMID: 27177394]
[5]
Little DG, Ramachandran M, Schindeler A. The anabolic and catabolic responses in bone repair. J Bone Joint Surg Br 2007; 89-B(4): 425-33.
[http://dx.doi.org/10.1302/0301-620X.89B4.18301] [PMID: 17463107]
[6]
Yan H, Liu X, Zhu M, et al. Hybrid use of combined and sequential delivery of growth factors and ultrasound stimulation in porous multilayer composite scaffolds to promote both vascularization and bone formation in bone tissue engineering. J Biomed Mater Res A 2016; 104(1): 195-208.
[http://dx.doi.org/10.1002/jbm.a.35556] [PMID: 26282063]
[7]
Oryan A, Alidadi S, Moshiri A, Maffulli N. Bone regenerative medicine: Classic options, novel strategies, and future directions. J Orthop Surg Res 2014; 9(1): 18.
[http://dx.doi.org/10.1186/1749-799X-9-18] [PMID: 24628910]
[8]
Calori GM, Mazza E, Colombo M, Ripamonti C. The use of bone-graft substitutes in large bone defects: Any specific needs? Injury 2011; 42(S2): S56-63.
[http://dx.doi.org/10.1016/j.injury.2011.06.011] [PMID: 21752369]
[9]
Arvidson K, Abdallah BM, Applegate LA, et al. Bone regeneration and stem cells. J Cell Mol Med 2011; 15(4): 718-46.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01224.x] [PMID: 21129153]
[10]
Xue N, Ding X, Huang R, et al. Bone tissue engineering in the treatment of bone defects. Pharmaceuticals 2022; 15(7): 879.
[http://dx.doi.org/10.3390/ph15070879] [PMID: 35890177]
[11]
Magadum MP, Yadav CMB, Phaneesha MS, Ramesh LJ. Acute compression and lengthening by the Ilizarov technique for infected nonunion of the tibia with large bone defects. J Orthop Surg 2006; 14(3): 273-9.
[http://dx.doi.org/10.1177/230949900601400308] [PMID: 17200528]
[12]
Kuznetsova D, Ageykin A, Koroleva A, et al. Surface micromorphology of cross-linked tetrafunctional polylactide scaffolds inducing vessel growth and bone formation. Biofabrication 2017; 9(2): 025009.
[http://dx.doi.org/10.1088/1758-5090/aa6725] [PMID: 28300041]
[13]
Tosounidis TH, Giannoudis PV. Biological facet of segmental bone loss reconstruction. J Orthop Trauma 2017; 31(5): S27-31.
[http://dx.doi.org/10.1097/BOT.0000000000000977] [PMID: 28938388]
[14]
Mauffrey C, Barlow BT, Smith W. Management of segmental bone defects. J Am Acad Orthop Surg 2015; 23(3): 143-53.
[PMID: 25716002]
[15]
Ogink PT, Teunissen FR, Massier JR, Raskin KA, Schwab JH, Lozano-Calderon SA. Allograft reconstruction of the humerus: Complications and revision surgery. J Surg Oncol 2019; 119(3): 329-35.
[http://dx.doi.org/10.1002/jso.25309] [PMID: 30517776]
[16]
Sohn HS, Oh JK. Review of bone graft and bone substitutes with an emphasis on fracture surgeries. Biomater Res 2019; 23(1): 9.
[http://dx.doi.org/10.1186/s40824-019-0157-y] [PMID: 30915231]
[17]
Wada K, Yu W, Elazizi M, et al. Locally delivered salicylic acid from a poly(anhydride-ester): Impact on diabetic bone regeneration. J Control Release 2013; 171(1): 33-7.
[http://dx.doi.org/10.1016/j.jconrel.2013.06.024] [PMID: 23827476]
[18]
Tevlin R, McArdle A, Atashroo D, et al. Biomaterials for craniofacial bone engineering. J Dent Res 2014; 93(12): 1187-95.
[http://dx.doi.org/10.1177/0022034514547271] [PMID: 25139365]
[19]
Quarto R, Giannoni P. Bone tissue engineering: Past-present-future. Methods Mol Biol 2016; 1416: 21-33.
[http://dx.doi.org/10.1007/978-1-4939-3584-0_2] [PMID: 27236664]
[20]
Campana V, Milano G, Pagano E, et al. Bone substitutes in orthopaedic surgery: From basic science to clinical practice. J Mater Sci Mater Med 2014; 25(10): 2445-61.
[http://dx.doi.org/10.1007/s10856-014-5240-2] [PMID: 24865980]
[21]
Soucacos PN, Dailiana Z, Beris AE, Johnson EO. Vascularised bone grafts for the management of non-union. Injury 2006; 37(S1): S41-50.
[http://dx.doi.org/10.1016/j.injury.2006.02.040]
[22]
Junqueira LC, Mescher A, Anthony L. Junqueira’s basic histology: text & atlas/Anthony L. New York: McGraw-Hill Medical 2013.
[23]
Kim HK, Moran ME, Salter RB. The potential for regeneration of articular cartilage in defects created by chondral shaving and subchondral abrasion. An experimental investigation in rabbits. J Bone Joint Surg Am 1991; 73(9): 1301-15.
[http://dx.doi.org/10.2106/00004623-199173090-00004] [PMID: 1918112]
[24]
Nesic D, Whiteside R, Brittberg M, Wendt D, Martin I, Mainilvarlet P. Cartilage tissue engineering for degenerative joint disease. Adv Drug Deliv Rev 2006; 58(2): 300-22.
[http://dx.doi.org/10.1016/j.addr.2006.01.012] [PMID: 16574268]
[25]
Sadri B, Nouraein S, Hossein-Khannazer N, Mohammadi J, Vosough M. Current and novel theranostic modalities for knee osteoarthritis. Jour 2021; 12(3): 17-30.
[26]
Peshkova M, Lychagin A, Lipina M, et al. Gender-related aspects in osteoarthritis development and progression: A review. Int J Mol Sci 2022; 23(5): 2767.
[http://dx.doi.org/10.3390/ijms23052767] [PMID: 35269906]
[27]
Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG. Outcomes of microfracture for traumatic chondral defects of the knee: Average 11-year follow-up. Arthroscopy 2003; 19(5): 477-84.
[http://dx.doi.org/10.1053/jars.2003.50112] [PMID: 12724676]
[28]
Bhosale AM, Richardson JB. Articular cartilage: Structure, injuries and review of management. Br Med Bull 2008; 87(1): 77-95.
[http://dx.doi.org/10.1093/bmb/ldn025] [PMID: 18676397]
[29]
Alford JW, Cole BJ. Cartilage restoration, part 2: Techniques, outcomes, and future directions. Am J Sports Med 2005; 33(3): 443-60.
[http://dx.doi.org/10.1177/0363546505274578] [PMID: 15716263]
[30]
Neovius E, Engstrand T. Craniofacial reconstruction with bone and biomaterials: Review over the last 11 years. J Plast Reconstr Aesthet Surg 2010; 63(10): 1615-23.
[http://dx.doi.org/10.1016/j.bjps.2009.06.003] [PMID: 19577527]
[31]
Baroli B. From natural bone grafts to tissue engineering therapeutics: Brainstorming on pharmaceutical formulative requirements and challenges. J Pharm Sci 2009; 98(4): 1317-75.
[http://dx.doi.org/10.1002/jps.21528] [PMID: 18729202]
[32]
Flierl MA, Smith WR, Mauffrey C, et al. Outcomes and complication rates of different bone grafting modalities in long bone fracture nonunions: A retrospective cohort study in 182 patients. J Orthop Surg Res 2013; 8(1): 33.
[http://dx.doi.org/10.1186/1749-799X-8-33] [PMID: 24016227]
[33]
Wang X, Thomsen P. Mesenchymal stem cell-derived small extracellular vesicles and bone regeneration. Basic Clin Pharmacol Toxicol 2021; 128(1): 18-36.
[http://dx.doi.org/10.1111/bcpt.13478] [PMID: 32780530]
[34]
Zhou Z, Zheng J, Meng X, Wang F. Effects of electrical stimulation on articular cartilage regeneration with a focus on piezoelectric biomaterials for articular cartilage tissue repair and engineering. Int J Mol Sci 2023; 24(3): 1836.
[http://dx.doi.org/10.3390/ijms24031836] [PMID: 36768157]
[35]
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331(14): 889-95.
[http://dx.doi.org/10.1056/NEJM199410063311401] [PMID: 8078550]
[36]
Knutsen G, Isaksen V, Johansen O, et al. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am 2007; 89(10): 2105-12.
[http://dx.doi.org/10.2106/00004623-200710000-00002] [PMID: 17908884]
[37]
Vanlauwe J, Saris DBF, Victor J, et al. Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: Early treatment matters. Am J Sports Med 2011; 39(12): 2566-74.
[http://dx.doi.org/10.1177/0363546511422220] [PMID: 21908720]
[38]
Davies R, Kuiper N. Regenerative medicine: A review of the evolution of autologous chondrocyte implantation (ACI) therapy. Bioengineering 2019; 6(1): 22.
[http://dx.doi.org/10.3390/bioengineering6010022] [PMID: 30871236]
[39]
Von Der Mark K, Gauss V, Von Der Mark H, Müller P. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature 1977; 267(5611): 531-2.
[http://dx.doi.org/10.1038/267531a0] [PMID: 559947]
[40]
Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A proof-of-concept clinical trial. Stem Cells 2014; 32(5): 1254-66.
[http://dx.doi.org/10.1002/stem.1634] [PMID: 24449146]
[41]
Peshkova M, Kosheleva N, Shpichka A, et al. Targeting inflammation and regeneration: Scaffolds, extracellular vesicles, and nanotechnologies as cell-free dual-target therapeutic strategies. Int J Mol Sci 2022; 23(22): 13796.
[http://dx.doi.org/10.3390/ijms232213796] [PMID: 36430272]
[42]
Ogura T, Mosier BA, Bryant T, Minas T. A 20-year follow-up after first-generation autologous chondrocyte implantation. Am J Sports Med 2017; 45(12): 2751-61.
[http://dx.doi.org/10.1177/0363546517716631] [PMID: 28745972]
[43]
Wood JJ, Malek MA, Frassica FJ, et al. Autologous cultured chondrocytes: Adverse events reported to the United States Food and Drug Administration. J Bone Joint Surg Am 2006; 88(3): 503-7.
[http://dx.doi.org/10.2106/00004623-200603000-00006] [PMID: 16510814]
[44]
Brittberg M. Autologous chondrocyte implantation-Technique and long-term follow-up. Injury 2008; 39(S1): 40-9.
[http://dx.doi.org/10.1016/j.injury.2008.01.040] [PMID: 18313471]
[45]
Lee CR, Grodzinsky AJ, Hsu HP, Martin SD, Spector M. Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee. J Orthop Res 2000; 18(5): 790-9.
[http://dx.doi.org/10.1002/jor.1100180517] [PMID: 11117302]
[46]
Gomoll AH, Probst C, Farr J, Cole BJ, Minas T. Use of a type I/III bilayer collagen membrane decreases reoperation rates for symptomatic hypertrophy after autologous chondrocyte implantation. Am J Sports Med 2009; 37(S1): 20S-3S.
[47]
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 2011; 19(7): 779-91.
[http://dx.doi.org/10.1016/j.joca.2011.02.010] [PMID: 21333744]
[48]
Anders S, Schaumburger J, Schubert T, Grifka J, Behrens P. Matrix-associated autologous chondrocyte transplantation (MACT). Minimally invasive technique in the knee. Oper Orthop Traumatol 2008; 20(3): 208-19.
[http://dx.doi.org/10.1007/s00064-008-1303-1] [PMID: 19169789]
[49]
Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 2000; (374): 212-34.
[http://dx.doi.org/10.1097/00003086-200005000-00020] [PMID: 10818982]
[50]
Anderer U, Libera J. In vitro engineering of human autogenous cartilage. J Bone Miner Res 2002; 17(8): 1420-9.
[http://dx.doi.org/10.1359/jbmr.2002.17.8.1420] [PMID: 12162496]
[51]
Hoburg A, Löer I, Körsmeier K, et al. Matrix-associated autologous chondrocyte implantation is an effective treatment at midterm follow-up in adolescents and young adults. Orthop J Sports Med 2019; 7(4): 2325967119841077.
[http://dx.doi.org/10.1177/2325967119841077] [PMID: 31041335]
[52]
Park YB, Ha CW, Lee CH, Yoon YC, Park YG. Cartilage regeneration in osteoarthritic patients by a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: Results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med 2017; 6(2): 613-21.
[http://dx.doi.org/10.5966/sctm.2016-0157] [PMID: 28191757]
[53]
Lim HC, Park YB, Ha CW, et al. Allogeneic umbilical cord blood-derived mesenchymal stem cell implantation versus microfracture for large, full-thickness cartilage defects in older patients: A multicenter randomized clinical trial and extended 5-year clinical follow-up. Orthop J Sports Med 2021; 9(1): 2325967120973052.
[http://dx.doi.org/10.1177/2325967120973052] [PMID: 33490296]
[54]
Amr M, Mallah A, Yasmeen S, et al. From chondrocytes to chondrons, maintenance of phenotype and matrix production in a composite 3D hydrogel scaffold. Gels 2022; 8(2): 90.
[http://dx.doi.org/10.3390/gels8020090] [PMID: 35200471]
[55]
Homma Y, Zimmermann G, Hernigou P. Cellular therapies for the treatment of non-union: The past, present and future. Injury 2013; 44(S1): S46-9.
[http://dx.doi.org/10.1016/S0020-1383(13)70011-1] [PMID: 23351871]
[56]
Sampson S, Bemden A, Aufiero D. Stem cell therapies for treatment of cartilage and bone disorders: osteoarthritis, avascular necrosis, and non-union fractures. PM R 2015; 7(4S): S26-32.
[http://dx.doi.org/10.1016/j.pmrj.2015.01.023] [PMID: 25864657]
[57]
White A, Wallis G. Endochondral ossification: A delicate balance between growth and mineralisation. Curr Biol 2001; 11(15): R589-91.
[http://dx.doi.org/10.1016/S0960-9822(01)00359-1] [PMID: 11516962]
[58]
Maes C, Kobayashi T, Selig MK, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 2010; 19(2): 329-44.
[http://dx.doi.org/10.1016/j.devcel.2010.07.010] [PMID: 20708594]
[59]
Kanczler JM, Oreffo ROC. Osteogenesis and angiogenesis: The potential for engineering bone. Eur Cell Mater 2008; 15: 100-14.
[http://dx.doi.org/10.22203/eCM.v015a08] [PMID: 18454418]
[60]
Marsell R, Einhorn TA. The biology of fracture healing. Injury 2011; 42(6): 551-5.
[http://dx.doi.org/10.1016/j.injury.2011.03.031] [PMID: 21489527]
[61]
Shirley D, Marsh D, Jordan G, McQuaid S, Li G. Systemic recruitment of osteoblastic cells in fracture healing. J Orthop Res 2005; 23(5): 1013-21.
[http://dx.doi.org/10.1016/j.orthres.2005.01.013] [PMID: 16140187]
[62]
Todeschi MR, El Backly R, Capelli C, et al. Transplanted umbilical cord mesenchymal stem cells modify the in vivo microenvironment enhancing angiogenesis and leading to bone regeneration. Stem Cells Dev 2015; 24(13): 1570-81.
[http://dx.doi.org/10.1089/scd.2014.0490] [PMID: 25685989]
[63]
Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell 2011; 9(1): 11-5.
[http://dx.doi.org/10.1016/j.stem.2011.06.008] [PMID: 21726829]
[64]
Zhuang WZ, Lin YH, Su LJ, et al. Mesenchymal stem/stromal cell-based therapy: Mechanism, systemic safety and biodistribution for precision clinical applications. J Biomed Sci 2021; 28(1): 28.
[http://dx.doi.org/10.1186/s12929-021-00725-7] [PMID: 33849537]
[65]
Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential. Trends Pharmacol Sci 2020; 41(9): 653-64.
[http://dx.doi.org/10.1016/j.tips.2020.06.009] [PMID: 32709406]
[66]
Zomorodian E, Eslaminejad BM. Mesenchymal stem cells as a potent cell source for bone regeneration. Stem Cells Int 2012; 2012: 1-9.
[http://dx.doi.org/10.1155/2012/980353] [PMID: 22448175]
[67]
Granero-Moltó F, Weis JA, Miga MI, et al. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells 2009; 27(8): 1887-98.
[http://dx.doi.org/10.1002/stem.103] [PMID: 19544445]
[68]
Sadri B, Tamimi A, Nouraein S, et al. Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report. Connect Tissue Res 2022; 63(6): 663-74.
[http://dx.doi.org/10.1080/03008207.2022.2074841] [PMID: 35856397]
[69]
Wittig O, Romano E, González C, et al. A method of treatment for nonunion after fractures using mesenchymal stromal cells loaded on collagen microspheres and incorporated into platelet-rich plasma clots. Int Orthop 2016; 40(5): 1033-8.
[http://dx.doi.org/10.1007/s00264-016-3130-6] [PMID: 26980620]
[70]
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 2022; 53(2): 399-407.
[http://dx.doi.org/10.1016/j.injury.2021.09.061] [PMID: 34670674]
[71]
Gao C, Seuntjens J, Kaufman GN, et al. Mesenchymal stem cell transplantation to promote bone healing. J Orthop Res 2012; 30(8): 1183-9.
[http://dx.doi.org/10.1002/jor.22028] [PMID: 22228593]
[72]
Liao Y, Zhang XL, Li L, Shen FM, Zhong MK. Stem cell therapy for bone repair: A systematic review and meta-analysis of preclinical studies with large animal models. Br J Clin Pharmacol 2014; 78(4): 718-26.
[http://dx.doi.org/10.1111/bcp.12382] [PMID: 24645974]
[73]
Jones EA, Giannoudis PV, Kouroupis D. Bone repair with skeletal stem cells: Rationale, progress to date and clinical application. Ther Adv Musculoskelet Dis 2016; 8(3): 57-71.
[http://dx.doi.org/10.1177/1759720X16642372] [PMID: 27247633]
[74]
Mott A, Mitchell A, McDaid C, et al. Systematic review assessing the evidence for the use of stem cells in fracture healing. Bone & Joint Open 2020; 1(10): 628-38.
[http://dx.doi.org/10.1302/2633-1462.110.BJO-2020-0129] [PMID: 33215094]
[75]
Killington K, Mafi R, Mafi P, Khan WS. A systematic review of clinical studies investigating mesenchymal stem cells for fracture non-union and bone defects. Curr Stem Cell Res Ther 2018; 13(4): 284-91.
[http://dx.doi.org/10.2174/1574888X12666170915121137] [PMID: 28914208]
[76]
Matas J, Orrego M, Amenabar D, et al. Umbilical cord-derived mesenchymal stromal cells (MSCs) for knee osteoarthritis: Repeated MSC dosing is superior to a single MSC dose and to hyaluronic acid in a controlled randomized phase I/II trial: Umbilical cord MSC for knee osteoarthritis. Stem Cells Transl Med 2019; 8(3): 215-24.
[http://dx.doi.org/10.1002/sctm.18-0053] [PMID: 30592390]
[77]
Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 2008; 11(3): 343-53.
[PMID: 18523506]
[78]
Xiang XN, Zhu SY, He HC, Yu X, Xu Y, He CQ. Mesenchymal stromal cell-based therapy for cartilage regeneration in knee osteoarthritis. Stem Cell Res Ther 2022; 13(1): 14.
[http://dx.doi.org/10.1186/s13287-021-02689-9] [PMID: 35012666]
[79]
Ha CW, Park YB, Kim SH, Lee HJ. Intra-articular mesenchymal stem cells in osteoarthritis of the knee: A systematic review of clinical outcomes and evidence of cartilage repair. Arthroscopy 2019; 35(1): 277-288.e2.
[http://dx.doi.org/10.1016/j.arthro.2018.07.028] [PMID: 30455086]
[80]
Lam J, Lu S, Lee EJ, et al. Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model. Osteoarthritis Cartilage 2014; 22(9): 1291-300.
[http://dx.doi.org/10.1016/j.joca.2014.06.035] [PMID: 25008204]
[81]
Dashtdar H, Rothan HA, Tay T, et al. A preliminary study comparing the use of allogenic chondrogenic pre-differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits. J Orthop Res 2011; 29(9): 1336-42.
[http://dx.doi.org/10.1002/jor.21413] [PMID: 21445989]
[82]
Ramezanifard R, Kabiri M, Ahvaz H. Effects of platelet rich plasma and chondrocyte co-culture on MSC chondrogenesis, hypertrophy and pathological responses. EXCLI J 2017; 16: 1031-45.
[PMID: 28900383]
[83]
Gu J, Wang B, Wang T, et al. Effects of cartilage progenitor cells, bone marrow mesenchymal stem cells and chondrocytes on cartilage repair as seed cells: An in vitro study. Drug Des Devel Ther 2022; 16: 1217-30.
[http://dx.doi.org/10.2147/DDDT.S356936] [PMID: 35509492]
[84]
Zhi Z, Zhang C, Kang J, et al. The therapeutic effect of bone marrow–derived mesenchymal stem cells on osteoarthritis is improved by the activation of the KDM6A/SOX9 signaling pathway caused by exposure to hypoxia. J Cell Physiol 2020; 235(10): 7173-82.
[http://dx.doi.org/10.1002/jcp.29615] [PMID: 32020624]
[85]
Saris TFF, de Windt TS, Kester EC, Vonk LA, Custers RJH, Saris DBF. Five-year outcome of 1-stage cell-based cartilage repair using recycled autologous chondrons and allogenic mesenchymal stromal cells: A first-in-human clinical trial. Am J Sports Med 2021; 49(4): 941-7.
[http://dx.doi.org/10.1177/0363546520988069] [PMID: 33591794]
[86]
Korpershoek JV, Vonk LA, Kester EC, et al. Efficacy of one-stage cartilage repair using allogeneic mesenchymal stromal cells and autologous chondron transplantation (IMPACT) compared to nonsurgical treatment for focal articular cartilage lesions of the knee: Study protocol for a crossover randomized controlled trial. Trials 2020; 21(1): 842.
[http://dx.doi.org/10.1186/s13063-020-04771-8] [PMID: 33036661]
[87]
Richardson JB, Wright KT, Wales J, et al. Efficacy and safety of autologous cell therapies for knee cartilage defects (autologous stem cells, chondrocytes or the two): Randomized controlled trial design. Regen Med 2017; 12(5): 493-501.
[http://dx.doi.org/10.2217/rme-2017-0032] [PMID: 28635368]
[88]
Muthu S, Jeyaraman M, Kotner MB, et al. Evolution of mesenchymal stem cell therapy as an Advanced Therapeutic Medicinal Product (ATMP)-an Indian perspective. Bioengineering 2022; 9(3): 111.
[http://dx.doi.org/10.3390/bioengineering9030111] [PMID: 35324800]
[89]
Iglesias-López C, Agustí A, Obach M, Vallano A. Regulatory framework for advanced therapy medicinal products in Europe and United States. Front Pharmacol 2019; 10: 921.
[http://dx.doi.org/10.3389/fphar.2019.00921] [PMID: 31543814]
[90]
Azuma K. Regulatory landscape of regenerative medicine in japan. Curr Stem Cell Rep 2015; 1(2): 118-28.
[http://dx.doi.org/10.1007/s40778-015-0012-6]
[91]
Durán CE, Cañás M, Urtasun MA, et al. Regulatory reliance to approve new medicinal products in Latin American and Caribbean countries. Rev Panam Salud Publica 2021; 45: 1-10.
[http://dx.doi.org/10.26633/RPSP.2021.10] [PMID: 33859678]
[92]
Courageous Innovation Available from:https://www.raps.org/regulatory-focus/news-articles/2015/4/the-essential-list-of-regulatory-authorities-in-asia#
[93]
Verified Clinical Benefit | Non-malignant Hematological, Neurological, and Other Disorder Indications Accelerated Approvals. Available from: https://www.fda.gov/drugs/accelerated-approval-program/verified-clinical-benefit-non-malignant-hematological-neurological-and-other-disorder-indications
[94]
Vericel Initiates Collaboration with Innovative Cellular Therapeutics. Available from: https://investors.vcel.com/news-releases/news-release-details/vericel-initiates-collaboration-innovative-cellular-therapeutics
[95]
ChondroCelect RSS. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/chondrocelect
[96]
Saris DBF, Vanlauwe J, Victor J, et al. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med 2008; 36(2): 235-46.
[http://dx.doi.org/10.1177/0363546507311095] [PMID: 18202295]
[97]
Saris DBF, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture: Characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 2009; 37(S1): 10S-9S.
[98]
MACI (Autologous Cultured Chondrocytes on a Porcine Collagen Membrane). Available from: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/maci-autologous-cultured-chondrocytes-porcine-collagen-membrane
[99]
Maci. Available from: https://www.ema.europa.eu/en/medicines/human/referrals/maci
[100]
A country where medicines are safe. Available from: https://nedrug.mfds.go.kr
[101]
Products. Available from: https://www.mfds.go.kr/eng/brd/m_19/list.do
[102]
Choi N-Y, Kim B-W, Yeo W-J, Kim H-B, Suh D-S, Kim J-S. Gel-type autologous chondrocyte (Chondron) implantation for treatment of articular cartilage defects of the knee. BMC Musculoskelet Disord 2010; 11: 103.
[103]
For patients. Available from: https://www.regrow.in/cartigrow-for-cartilage-damage
[104]
Review Reports: Regenerative Medical Products. Available from: https://www.pmda.go.jp/english/review-services/reviews/approved-information/0004.html
[105]
Spherox. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/spherox
[106]
Armoiry X, Cummins E, Connock M, et al. Autologous chondrocyte implantation with Chondrosphere for treating articular cartilage defects in the knee: An evidence review group perspective of a NICE single technology appraisal. PharmacoEconomics 2019; 37(7): 879-86.
[http://dx.doi.org/10.1007/s40273-018-0737-z] [PMID: 30426462]
[107]
Cellular Therapies - Chondrocytes - T - Ortho-ACI - Orthocell Ltd - Suspension - Vial (289402). Available from: https://www.tga.gov.au/resources/artg/289402
[108]
Regeneration of human cartilage. 2022. Available from: https://orthocell.com/orthoaci
[109]
Aesculap biologics, LLC. Available from: https://www. aesculapbiologics.com
[110]
Mesestrocell- Cell therapy for osteoarthritis. Available from: http://en.celltech.ir/mesestrocell-cell-therapy-for-osteoarthritis/
[111]
Mfds.go.kr. Available from: https://www.mfds.go.kr/eng/brd/m_30/view.do?seq=70954
[112]
OSSGROW - for patients. Available from: https://www. ossgrow.com
[113]
Schneider CK, Salmikangas P, Jilma B, et al. Challenges with advanced therapy medicinal products and how to meet them. Nat Rev Drug Discov 2010; 9(3): 195-201.
[http://dx.doi.org/10.1038/nrd3052] [PMID: 20190786]
[114]
Grossman AD, Den Haese JP Jr, Georger L, Mc Millan S, Tuck JA. Matrix-induced Autologous Chondrocyte Implantation (MACI) is largely effective and provides significant improvement in patients with symptomatic, large chondral defects: A systematic review and meta-analysis. Surg Technol Int 2022; 41: 41.
[http://dx.doi.org/10.52198/22.STI.41.OS1613] [PMID: 35920337]
[115]
Ocugen inc. - patient-centric biotechnology 2022. Available from: https://ocugen.com
[116]
Song Y, Du H, Dai C, et al. Human adipose-derived mesenchymal stem cells for osteoarthritis: A pilot study with long-term follow-up and repeated injections. Regen Med 2018; 13(3): 295-307.
[http://dx.doi.org/10.2217/rme-2017-0152] [PMID: 29417902]
[117]
Qiao Z, Tang J, Yue B, et al. Human adipose-derived mesenchymal progenitor cells plus microfracture and hyaluronic acid for cartilage repair: A Phase IIa trial. Regen Med 2020; 15(1): 1193-214.
[http://dx.doi.org/10.2217/rme-2019-0068] [PMID: 32043426]
[118]
Lu L, Dai C, Zhang Z, et al. Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: A prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem Cell Res Ther 2019; 10(1): 143.
[http://dx.doi.org/10.1186/s13287-019-1248-3] [PMID: 31113476]
[119]
Gupta PK, Chullikana A, Rengasamy M, et al. Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): Preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Res Ther 2016; 18(1): 301.
[http://dx.doi.org/10.1186/s13075-016-1195-7] [PMID: 27993154]
[120]
Chen CF, Hu CC, Wu CT, et al. Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: A phase I/II, randomized, active-control, single-blind, multiple-center clinical trial. Stem Cell Res Ther 2021; 12(1): 562.
[http://dx.doi.org/10.1186/s13287-021-02631-z] [PMID: 34717765]
[121]
Lew S, Cho J, Kim T, Lee M. Long-term follow-up assessment of the safety and efficacy of INVOSSA-K INJ., a novel cell mediated gene therapy for treatment of osteoarthritis. Osteoarthritis Cartilage 2019; 27: S212.
[http://dx.doi.org/10.1016/j.joca.2019.02.330]
[122]
Talesa G, Manfreda F, Pace V, et al. The treatment of knee cartilage lesions: State of the art. Acta Biomed 2022; 93(4): e2022099.
[PMID: 36043984]
[123]
Jayankura M, Schulz AP, Delahaut O, et al. Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: A pilot study. Stem Cell Res Ther 2021; 12(1): 363.
[http://dx.doi.org/10.1186/s13287-021-02432-4] [PMID: 34174963]

Rights & Permissions Print Cite
Article Metrics
19
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy