Primary Chondroprogenitors: Standardized & Versatile Allogeneic Cytotherapeutics: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Catherine Yang and Version 1 by Alexis Laurent.

Primary chondroprogenitors obtained from standardized cell sources (e.g., FE002 clinical grade cell sources) may be cultured in vitro and may be cytotherapeutically applied in allogeneic musculoskeletal regenerative medicine. Multicentric translational research on FE002 human primary chondroprogenitors under the Swiss progenitor cell transplantation program has notably validated their robustness and high versatility for therapeutic formulation in clinically compatible prototypes, as well as a good safety profile in diverse in vivo preclinical models. Therein, stringently controlled primary cell source establishment and extensive cell manufacturing optimization have technically confirmed the adequation of FE002 primary chondroprogenitors with standard industrial biotechnology workflows for consistent diploid cell biobanking under GMP. Laboratory characterization studies and extensive qualification work on FE002 progenitor cell sources have elucidated the key and critical attributes of the cellular materials of interest for potential and diversified human cytotherapeutic uses. Multiple formulation studies (i.e., hydrogel-based standardized transplants, polymeric-scaffold-based tissue engineering products) have shown the high versatility of FE002 primary chondroprogenitors, for the obtention of functional allogeneic cytotherapeutics. Multiple in vivo preclinical studies (e.g., rodent models, GLP goat model) have robustly documented the safety of FE002 primary chondroprogenitors following implantation. Clinically, FE002 primary chondroprogenitors may potentially be used in various forms for volumetric tissue replacement (e.g., treatment of large chondral/osteochondral defects of the knee) or for the local management of chondral affections and pathologies (i.e., injection use in mild to moderate osteoarthritis cases). Overall, standardized FE002 primary chondroprogenitors as investigated under the Swiss progenitor cell transplantation program were shown to constitute tangible contenders in novel human musculoskeletal regenerative medicine approaches, for versatile and safe allogeneic clinical cytotherapeutic management. 

  • bioengineering
  • chondral/osteochondral defects
  • chondrogenesis
  • cytotherapeutics
  • formulation
  • musculoskeletal pathologies
  • primary FE002 chondroprogenitors
  • regenerative medicine
  • safety
  • translational research
Musculoskeletal diseases in general and chondral/osteochondral affections, in particular, are highly incident in aging patient populations [1,2,3,4][1][2][3][4]. While conservative orthopedic best practices enable the successful clinical management of critical cases of cartilage injury or degeneration (e.g., prosthetic replacement), effective regenerative medicine interventions and solutions are necessary in the cases of moderate to severe affections [3,5,6,7,8][3][5][6][7][8]. Therefore, many natural and artificial biomaterials or bioengineered constructs have been successfully clinically applied for chondropathies and cartilage tissue defects, with extensive available hindsight (i.e., intervention safety, quality, efficacy) [5,9,10,11,12,13,14,15,16,17,18][5][9][10][11][12][13][14][15][16][17][18]. Parallelly, important translational efforts, deployed over the past 40 years, have led to the implementation of diverse clinical protocols for several generations of autologous chondrocyte implantation (ACI) [1,4,8,19,20,21,22,23,24,25,26,27,28][1][4][8][19][20][21][22][23][24][25][26][27][28]. While initial and successful approaches to ACI may have relied on the use of cultured cells or minimally manipulated chondrocyte suspensions, current commercially available clinical approaches to cartilage regenerative medicine often comprise the use of a matrix/scaffold component (i.e., combination products, e.g., cells in a hyaluronan-based hydrogel scaffold or bilayer collagen constructs) [1,10,11,28,29,30,31,32,33,34,35,36,37][1][10][11][28][29][30][31][32][33][34][35][36][37].
Vast arrays of potential cell sources (e.g., various stem and progenitor cells, somatic cells, platelets, etc.) and processing methods (e.g., preparation of cell suspensions, spheroids) have been investigated for the high-quality cytotherapeutic management of chondropathies and chondral/osteochondral defects [7,11,38,39,40,41,42][7][11][38][39][40][41][42]. Recently, multiple genetically modified cell lines, designed for enhanced chondrogenic function, have been studied and clinically proposed for cartilage tissue engineering [6,43,44,45][6][43][44][45]. From a technical standpoint, the scientific knowledge of the in vitro behavior and functional evolution (i.e., transiently reduced chondrogenesis potential in monolayer cellular expansion) of cultured chondrocytes has rapidly increased [5,8,14,31,46,47,48,49,50,51,52,53,54,55][5][8][14][31][46][47][48][49][50][51][52][53][54][55]. For therapeutic cell manufacturing purposes, numerous studies have enabled and have validated (i.e., from technical, quality, and functional standpoints) the substitution of fetal bovine serum (FBS) by human platelet lysates (HPL) as cellular growth medium supplements [28,56,57,58,59,60,61,62,63][28][56][57][58][59][60][61][62][63]. Notwithstanding, despite enormous progress in the biotechnological and bioengineering approaches to cell-based combination products for cartilage repair and regeneration, important regulatory and clinical bottlenecks have recently been documented [28,40,64,65,66,67,68,69,70][28][40][64][65][66][67][68][69][70]. Indeed, specific quality-oriented and process-based approaches to cell therapy manufacturing have become the norm (e.g., application of cGMPs for cellular active substances and finished cell-based product manufacture) [28]. Importantly from the clinical standpoint, the cartilage lesion localization, the surgical approach, and the patient follow-up management plan have been identified as critical factors for consistently attaining long-term clinical success with cytotherapies for cartilage tissue affections [14,65,69][14][65][69].
Human primary chondroprogenitors (e.g., FE002 clinical grade cell sources) have been extensively investigated under the Swiss progenitor cell transplantation program as a potential cytotherapeutic solution for the optimal homologous allogeneic management of diverse cartilage tissue disorders [38,71,72][38][71][72]. Human FE002 primary chondroprogenitors are cultured diploid cells, inherently pre-terminally differentiated, which display monomodal and stable phenotypes in vitro [38,72][38][72]. Homogeneous and robust cryopreserved cell banks and cell lots of FE002 primary chondroprogenitors may be exploited as highly sustainable tools and material sources for allogeneic musculoskeletal cytotherapeutic applications under modern restrictive quality requirements [71,72][71][72]. Importantly, human FE002 primary chondroprogenitors are highly biocompatible with diverse biomaterials, possess an inherent immune privilege, and present no known tumorigenic behaviors [38,72][38][72].
Such standardized biological materials are biotechnologically manufactured and are formulated following best practices in pharmaceutical sciences and cell-based bioengineering, with the central therapeutic objectives of rapidly and optimally restoring chondral tissular structures and functions [72]. Overall, the FE002 primary chondroprogenitors investigated under the Swiss progenitor cell transplantation program were shown to present high robustness and versatility in an array of potential therapeutic uses (e.g., fresh or off-the-freezer cell therapies) in human musculoskeletal regenerative medicine [71,72][71][72]. A succinct overview of the currently published body of knowledge (i.e., scientific peer-reviewed elements) on FE002 primary chondroprogenitors is presented in Table 1.
Table 1. Summary of the published peer-reviewed reports describing the collaborative and multicentric translational work (i.e., characterization, qualification, validation) on FE002 primary chondroprogenitors under the Swiss progenitor cell transplantation program. This constantly evolving body of knowledge has established FE002 primary chondroprogenitors as standardized and versatile cytotherapeutic contenders for human musculoskeletal regenerative medicine, for repair promotion and/or regeneration support in chondral/osteochondral affections. CAM, chorioallantoic membrane model; GLP, good laboratory practices; HA, hyaluronic acid.
Study Subject/Domain Scope of the Study/Investigated Parameters/Main Data References
1. Progenitor Cell Source Establishment Biological starting material procurement (i.e., controlled organ donation within the Swiss progenitor cell transplantation program) and establishment of FE002 primary progenitor cell sources in a cryogenically preserved multi-tiered cell bank system. [71]
2. In Vitro Cell Type Characterization Characterization of progenitor cell type key and critical attributes (e.g., cellular proliferative behavior in culture, cellular lot homogeneity and purity, cell genetic and phenotypic stability, proteomics, chondrogenic potential, in vitro safety parameters). [38,72][38][72]
3. Characterization of In Vitro Mechanobiological Cellular Behavior Study of the influence of physical (i.e., mechanical) parameters on cellular biology and functional attributes 1. Optimization of physical processing workflows for cytotherapeutic material lots. [73,74,75][73][74][75]
4. In Vitro Cell Banking & Biotechnological Manufacturing Optimization and standardization of in vitro progenitor cell manufacturing workflows (i.e., industrial-scale cellular lots). Confirmation of progenitor cell source sustainability at passage levels for clinical use 2. [72]
5. Formulation Studies for Functional Cytotherapeutic Products Formulation and translational characterization/qualification of hydrogel-based (e.g., modified HA-based gels) standardized transplants and polymeric scaffold-based tissue engineering products yielding viable/functional progenitor cells. [76,77,78,79,80][76][77][78][79][80]
6. In Vivo Preclinical Safety Assessments Study of progenitor cellular material or cytotherapeutic combination product safety in ovo (i.e., standardized CAM model) and in vivo (e.g., subcutaneous rodent implantation models, GLP study of knee chondral defect management in goats). [72,76,77,79][72][76][77][79]
1 It is noteworthy that the considered tissue engineering products/prototypes were reported to be characterized by endpoint mechanical attributes which did not match those of native chondral tissues. This aspect has not been interpreted negatively, based on the fact that such orthopedic cell-based approaches aim to stimulate repair and/or support regeneration processes, rather than exclusively structurally replacing the damaged cartilage. Therefore, while the implanted constructs must be able to bare weight, sufficient potential for mechanical adaptation to the local healing environment must remain, for optimal graft integration and therapeutic deployment of functional attributes. 2 The established models have outlined that a single clinical grade primary chondroprogenitor cell source could potentially yield several million therapeutic bioengineered cartilage grafts or injectable viable cell suspensions, without the need for repetition of the cell type establishment phase.
Notably, multiple in vivo preclinical studies (e.g., in rodent and goat models) have robustly documented the safety of FE002 primary chondroprogenitors following implantation, which may therefore be safely considered for investigational human cytotherapeutic use (i.e., international first-in-man clinical trials) [72,76,77,79][72][76][77][79]. From a clinical indication standpoint, such cellular materials and combinations thereof may potentially be used for volumetric tissue replacement (e.g., treatment of extensive chondral/osteochondral defects of the knee) or the local management of mild to moderate chondral affections and pathologies (i.e., injectable hydrogels in osteoarthritis patients) [72]. Overall, the aggregated multicentric translational work on FE002 primary progenitor cell sources, performed over the past decade in Switzerland, has confirmed their high versatility and safety for application as cellular active ingredients within the development of novel cytotherapeutic products and standardized transplants for human use (Table 1) [38,72,76,77,78,79,80][38][72][76][77][78][79][80].

References

  1. 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, 889–895.
  2. Bedi, A.; Feeley, B.T.; Williams, R.J. Management of articular cartilage defects of the knee. J. Bone Jt. Surg. Am. 2010, 92, 994–1009.
  3. Urlic, I.; Ivkovic, A. Cell sources for cartilage repair-biological and clinical perspective. Cells 2021, 10, 2496.
  4. Martin, R.; Laurent, A.; Applegate, L.A.; Philippe, V. Grands défects chondraux et ostéochondraux du genou: Traitement par greffe chondrocytaire autologue. Rev. Med. Suisse 2022, 18, 2384–2390.
  5. Makris, E.A.; Gomoll, A.H.; Malizos, K.N.; Hu, J.C.; Athanasiou, K.A. Repair and tissue engineering techniques for articular cartilage. Nat. Rev. Rheumatol. 2015, 11, 21–34.
  6. Cherian, J.J.; Parvizi, J.; Bramlet, D.; Lee, K.H.; Romness, D.W.; Mont, M.A. Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-B1 in patients with grade 3 chronic degenerative joint disease of the knee. Osteoarthr. Cartil. 2015, 23, 2109–2118.
  7. Teo, A.Q.A.; Wong, K.L.; Shen, L.; Lim, J.Y.; Wei, S.T.; Lee, H.; Hui, J.H.P. Equivalent 10-year outcomes after implantation of autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation for chondral defects of the knee. Am. J. Sport. Med. 2019, 47, 2881–2887.
  8. Asnaghi, M.A.; Power, L.; Barbero, A.; Haug, M.; Köppl, R.; Wendt, D.; Martin, I. Biomarker signatures of quality for engineering nasal chondrocyte-derived cartilage. Front. Bioeng. Biotechnol. 2020, 8, 283.
  9. Ehlers, E.M.; Fuss, M.; Rohwedel, J.; Russlies, M.; Kühnel, W.; Behrens, P. Development of a biocomposite to fill out articular cartilage lesions. Light, scanning and transmission electron microscopy of sheep chondrocytes cultured on a collagen I/III sponge. Ann. Anat. 1999, 181, 513–518.
  10. Marcacci, M.; Berruto, M.; Brocchetta, D.; Delcogliano, A.; Ghinelli, D.; Gobbi, A.; Kon, E.; Pederzini, L.; Rosa, D.; Sacchetti, G.L.; et al. Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin. Orthop. Rel. Res. 2005, 435, 96–105.
  11. Dhollander, A.A.; Verdonk, P.C.; Lambrecht, S.; Verdonk, R.; Elewaut, D.; Verbruggen, G.; Almqvist, K.F. Midterm results of the treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes. Am. J. Sport. Med. 2012, 40, 75–82.
  12. Marlovits, S.; Aldrian, S.; Wondrasch, B.; Zak, L.; Albrecht, C.; Welsch, G.; Trattnig, S. Clinical and radiological outcomes 5 years after matrix-induced autologous chondrocyte implantation in patients with symptomatic, traumatic chondral defects. Am. J. Sport. Med. 2012, 40, 2273–2280.
  13. Brix, M.O.; Stelzeneder, D.; Chiari, C.; Koller, U.; Nehrer, S.; Dorotka, R.; Windhager, R.; Domayer, S.E. Treatment of full-thickness chondral defects with Hyalograft C in the knee: Long-term results. Am. J. Sport. Med. 2014, 42, 1426–1432.
  14. Kon, E.; Roffi, A.; Filardo, G.; Tesei, G.; Marcacci, M. Scaffold-based cartilage treatments: With or without cells? A systematic review of preclinical and clinical evidence. Arthroscopy 2015, 31, 767–775.
  15. Brittberg, M.; Gomoll, A.H.; Canseco, J.A.; Far, J.; Lind, M.; Hui, J. Cartilage repair in the degenerative ageing knee. Acta Orthop. 2016, 87, 26–38.
  16. Kon, E.; Filardo, G.; Brittberg, M.; Busacca, M.; Condello, V.; Engebretsen, L.; Marlovits, S.; Niemeyer, P.; Platzer, P.; Posthumus, M.; et al. A multilayer biomaterial for osteochondral regeneration shows superiority vs. microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years. Knee Surg. Sport. Traumatol. Arthrosc. 2018, 26, 2704–2715.
  17. Binder, H.; Hoffman, L.; Zak, L.; Tiefenboeck, T.; Aldrian, S.; Albrecht, C. Clinical evaluation after matrix-associated autologous chondrocyte transplantation: A comparison of four different graft types. Bone Jt. Res. 2021, 10, 370–379.
  18. Porcello, A.; Laurent, A.; Hirt-Burri, N.; Abdel-Sayed, P.; de Buys Roessingh, A.; Raffoul, W.; Jordan, O.; Allémann, E.; Applegate, L.A. Hyaluronan-based hydrogels as functional vectors for standardized therapeutics in tissue engineering and regenerative medicine. In Nanopharmaceuticals in Regenerative Medicine; CRC Press: Boca Raton, FL, USA, 2022.
  19. 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. Rel. Res. 2000, 374, 212–234.
  20. Harris, J.D.; Siston, R.A.; Pan, X.; Flanigan, D.C. Autologous chondrocyte implantation: A systematic review. J. Bone Jt. Surg. 2010, 92, 2220–2233.
  21. Peterson, L.; Vasiliadis, H.S.; Brittberg, M.; Lindahl, A. Autologous chondrocyte implantation: A long-term follow-up. Am. J. Sport. Med. 2010, 38, 1117–1124.
  22. Bentley, G.; Biant, L.C.; Vijayan, S.; Macmull, S.; Skinner, J.A.; Carrington, R.W. Minimum ten-year results of a prospective randomised study of autologous chondrocyte implantation versus mosaicplasty for symptomatic articular cartilage lesions of the knee. J. Bone Jt. Surg. 2012, 94, 504–509.
  23. Biant, L.C.; Bentley, G.; Vijayan, S.; Skinner, J.A.; Carrington, R.W. Long-term results of autologous chondrocyte implantation in the knee for chronic chondral and osteochondral defects. Am. J. Sport. Med. 2014, 42, 2178–2183.
  24. Nawaz, S.Z.; Bentley, G.; Briggs, T.W.; Carrington, R.W.; Skinner, J.A.; Gallagher, K.R.; Dhinsa, B.S. Autologous chondrocyte implantation in the knee: Mid-term to long-term results. J. Bone Jt. Surg. 2014, 96, 824–830.
  25. Oussedik, S.; Tsitskaris, K.; Parker, D. Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: A systematic review. Arthroscopy 2015, 31, 732–744.
  26. Mumme, M.; Barbero, A.; Miot, S.; Wixmerten, A.; Feliciano, S.; Wolf, F.; Asnaghi, A.M.; Baumhoer, D.; Bieri, O.; Kretzcchmar, M.; et al. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: An observational first-in-human trial. Lancet 2016, 388, 1985–1994.
  27. Davies, R.L.; Kuiper, N.J. Regenerative medicine: A review of the evolution of autologous chondrocyte implantation (ACI) therapy. Bioengineering 2019, 6, 22.
  28. Philippe, V.; Laurent, A.; Hirt-Burri, N.; Abdel-Sayed, P.; Scaletta, C.; Schneebeli, V.; Michetti, M.; Brunet, J.-F.; Applegate, L.A.; Martin, R. Retrospective analysis of autologous chondrocyte-based cytotherapy production for clinical use: GMP process-based manufacturing optimization in a Swiss university hospital. Cells 2022, 11, 1016.
  29. Abelow, S.P.; Guillen, P.; Ramos, T. Arthroscopic technique for matrix-induced autologous chondrocyte implantation for the treatment of large chondral defects in the knee and ankle. Op. Tech. Orthop. 2006, 16, 257–261.
  30. Brittberg, M. Cell carriers as the next generation of cell therapy for cartilage repair: A review of the matrix-induced autologous chondrocyte implantation procedure. Am. J. Sport. Med. 2010, 38, 1259–1271.
  31. Albrecht, C.; Tichy, B.; Nürnberger, S.; Hosiner, S.; Zak, L.; Aldrian, S.; Marlovits, S. Gene expression and cell differentiation in matrix-associated chondrocyte transplantation grafts: A comparative study. Osteoarthr. Cart. 2011, 19, 1219–1227.
  32. Flohé, S.; Betsch, M.; Ruße, K.; Wild, M.; Windolf, J.; Schulz, M. Comparison of two different matrix-based autologous chondrocyte transplantation systems: 1 year follow-up results. Eur. J. Trauma Emerg. Surg. 2011, 37, 397–403.
  33. Cortese, F.; McNicholas, M.; Janes, G.; Gillogly, S.; Abelow, S.P.; Gigante, A.; Coletti, N. Arthroscopic delivery of matrix-induced autologous chondrocyte implant: International experience and technique recommendations. Cartilage 2012, 3, 156–164.
  34. Crawford, D.C.; DeBerardino, T.M.; Williams, R.J., 3rd. NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: An FDA phase-II prospective, randomized clinical trial after two years. J. Bone Jt. Surg. 2012, 94, 979–989.
  35. Vijayan, S.; Bartlett, W.; Bentley, G.; Carrington, R.W.; Skinner, J.A.; Pollock, R.C.; Alorjani, M.; Briggs, T.W. Autologous chondrocyte implantation for osteochondral lesions in the knee using a bilayer collagen membrane and bone graft: A two- to eight-year follow-up study. J. Bone Jt. Surg. 2012, 94, 488–492.
  36. McCarthy, H.S.; Roberts, S. A histological comparison of the repair tissue formed when using either Chondrogide(®) or periosteum during autologous chondrocyte implantation. Osteoarthr. Cart. 2013, 21, 2048–2057.
  37. Li, X.; Li, S.; Qian, J.; Chen, Y.; Zhou, Y.; Fu, P. Early efficacy of type I collagen-based matrix-assisted autologous chondrocyte transplantation for the treatment of articular cartilage lesions. Front. Bioeng. Biotechnol. 2021, 9, 760179.
  38. Darwiche, S.E.; Scaletta, C.; Raffoul, W.; Pioletti, D.P.; Applegate, L.A. Epiphyseal chondroprogenitors provide a stable cell source for cartilage cell therapy. Cell Med. 2012, 4, 23–32.
  39. Pelttari, K.; Pippenger, B.; Mumme, M.; Feliciano, S.; Scotti, C.; Mainil-Varlet, P.; Procino, A.; von Rechenberg, B.; Schwamborn, T.; Jakob, M.; et al. Adult human neural crest-derived cells for articular cartilage repair. Sci. Transl. Med. 2014, 6, 251ra119.
  40. Huang, B.J.; Hu, J.C.; Athanasiou, K.A. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials 2016, 98, 1–22.
  41. Mortazavi, F.; Shafaei, H.; Soleimani Rad, J.; Rushangar, L.; Montaceri, A.; Jamshidi, M. High quality of infant chondrocytes in comparison with adult chondrocytes for cartilage tissue engineering. World J. Plast. Surg. 2017, 6, 183–189.
  42. Hoburg, A.; Niemeyer, P.; Laute, V.; Zinser, W.; Becher, C.; Kolombe, T.; Fay, J.; Pietsch, S.; Kuźma, T.; Widuchowski, W.; et al. Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture. Knee Surg. Sport. Traumatol. Arthrosc. 2023, 31, 2482–2493.
  43. Ha, C.-W.; Noh, M.J.; Choi, K.B.; Lee, K.H. Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients. Cytotherapy 2012, 14, 247–256.
  44. Tritschler, H.; Fischer, K.; Seissler, J.; Fiedler, J.; Halbgebauer, R.; Huber-Lang, M.; Schnieke, A.; Brenner, R.E. New insights into xenotransplantation for cartilage repair: Porcine multi-genetically modified chondrocytes as a promising cell source. Cells 2021, 10, 2152.
  45. Evans, C.H.; Ghivizzani, S.C.; Robbins, P.D. Orthopaedic gene therapy: Twenty-five years on. JBJS Rev. 2021, 9, e20.
  46. Manning, W.K.; Bonner, W.M., Jr. Isolation and culture of chondrocytes from human adult articular cartilage. Arthritis Rheum. 1967, 10, 235–239.
  47. Tallheden, T.; Karlsson, C.; Brunner, A.; Van Der Lee, J.; Hagg, R.; Tommasini, R.; Lindahl, A. Gene expression during redifferentiation of human articular chondrocytes. Osteoarthr. Cart. 2004, 12, 525–535.
  48. Kang, S.W.; Yoo, S.P.; Kim, B.S. Effect of chondrocyte passage number on histological aspects of tissue-engineered cartilage. Bio-Med. Mat. Eng. 2007, 17, 269–276.
  49. Martinez, I.; Elvenes, J.; Olsen, R.; Bertheussen, K.; Johansen, O. Redifferentiation of in vitro expanded adult articular chondrocytes by combining the hanging-drop cultivation method with hypoxic environment. Cell Transplant. 2008, 17, 987–996.
  50. Lin, Z.; Fitzgerald, J.B.; Xu, J.; Willers, C.; Wood, D.; Grodzinsky, A.J.; Zheng, M.H. Gene expression profiles of human chondrocytes during passaged monolayer cultivation. J. Orthop. Res. 2008, 26, 1230–1237.
  51. Enochson, L.; Brittberg, M.; Lindahl, A. Optimization of a chondrogenic medium through the use of factorial design of experiments. BioRes Open Access 2012, 1, 306–313.
  52. Oseni, A.O.; Butler, P.E.; Seifalian, A.M. Optimization of chondrocyte isolation and characterization for large-scale cartilage tissue engineering. J. Surg. Res. 2013, 181, 41–48.
  53. Chijimatsu, R.; Kobayashi, M.; Ebina, K.; Iwahashi, T.; Okuno, Y.; Hirao, M.; Fukuhara, A.; Nakamura, N.; Yoshikawa, H. Impact of dexamethasone concentration on cartilage tissue formation from human synovial derived stem cells in vitro. Cytotechnology 2018, 70, 819–829.
  54. Kisiday, J.D. Expansion of chondrocytes for cartilage tissue engineering: A review of chondrocyte dedifferentiation and redifferentiation as a function of growth in expansion culture. Regen. Med. Front. 2020, 2, e200002.
  55. Chen, Y.; Yu, Y.; Wen, Y.; Chen, J.; Lin, J.; Sheng, Z.; Zhou, W.; Sun, H.; An, C.; Chen, J.; et al. A high-resolution route map reveals distinct stages of chondrocyte dedifferentiation for cartilage regeneration. Bone Res. 2022, 10, 38.
  56. Mandl, E.W.; van der Veen, S.W.; Verhaar, J.A.; van Osch, G.J. Serum-free medium supplemented with high-concentration FGF2 for cell expansion culture of human ear chondrocytes promotes redifferentiation capacity. Tissue Eng. 2002, 8, 573–580.
  57. Gaissmaier, C.; Fritz, J.; Krackhardt, T.; Flesch, I.; Aicher, W.K.; Ashammakhi, N. Effect of human platelet supernatant on proliferation and matrix synthesis of human articular chondrocytes in monolayer and three-dimensional alginate cultures. Biomaterials 2005, 26, 1953–1960.
  58. Hildner, F.; Eder, M.J.; Hofer, K.; Aberl, J.; Redl, H.; van Griensven, M.; Gabriel, C.; Peterbauer-Scherb, A. Human platelet lysate successfully promotes proliferation and subsequent chondrogenic differentiation of adipose-derived stem cells: A comparison with articular chondrocytes. J. Tissue Eng. Regen. Med. 2015, 9, 808–818.
  59. Sykes, J.G.; Kuiper, J.H.; Richardson, J.B.; Roberts, S.; Wright, K.T.; Kuiper, N.J. Impact of human platelet lysate on the expansion and chondrogenic capacity of cultured human chondrocytes for cartilage cell therapy. Eur. Cell Mater. 2018, 35, 255–267.
  60. Rikkers, M.; Levato, R.; Malda, J.; Vonk, L.A. Importance of timing of platelet lysate-supplementation in expanding or redifferentiating human chondrocytes for chondrogenesis. Front. Bioeng. Biotechnol. 2020, 8, 804.
  61. Philippe, V.; Laurent, A.; Abdel-Sayed, P.; Hirt-Burri, N.; Applegate, L.A.; Martin, R. Human platelet lysate as an alternative to autologous serum for human chondrocyte clinical use. Cartilage 2021, 13, 509S–518S.
  62. Kachroo, U.; Zachariah, S.M.; Thambaiah, A.; Tabasum, A.; Livingston, A.; Rebekah, G.; Srivastava, A.; Vinod, E. Comparison of human platelet lysate versus fetal bovine serum for expansion of human articular cartilage-derived chondroprogenitors. Cartilage 2021, 13, 107S–116S.
  63. Liau, L.L.; Hassan, M.N.F.b.; Tang, Y.L.; Ng, M.H.; Law, J.X. Feasibility of human platelet lysate as an alternative to fetal bovine serum for in vitro expansion of chondrocytes. Int. J. Mol. Sci. 2021, 22, 1269.
  64. Johnson, P.C.; Bertram, T.A.; Tawil, B.; Hellman, K.B. Hurdles in tissue engineering/regenerative medicine product commercialization: A survey of North American academia and industry. Tissue Eng. Part A 2011, 17, 5–15.
  65. Harris, J.D.; Siston, R.A.; Brophy, R.H.; Lattermann, C.; Carey, J.L.; Flanigan, D.C. Failures, re-operations, and complications after autologous chondrocyte implantation--A systematic review. Osteoarthr. Cart. 2011, 19, 779–791.
  66. Pearce, K.F.; Hildebrandt, M.; Greinix, H.; Scheding, S.; Koehl, U.; Worel, N.; Apperley, J.; Edinger, M.; Hauser, A.; Mischak-Weissinger, E.; et al. Regulation of advanced therapy medicinal products in Europe and the role of academia. Cytotherapy 2014, 16, 289–297.
  67. Ikawa, T.; Yano, K.; Watanabe, N.; Masamune, K.; Yamato, M. Non-clinical assessment design of autologous chondrocyte implantation products. Regen. Ther. 2015, 1, 98–108.
  68. Ramezankhani, R.; Torabi, S.; Minaei, N.; Madani, H.; Rezaeiani, S.; Hassani, S.N.; Gee, A.P.; Dominici, M.; Silva, D.N.; Baharvand, H.; et al. Two decades of global progress in authorized advanced therapy medicinal products: An emerging revolution in therapeutic strategies. Front. Cell Develop. Biol. 2020, 8, 547653.
  69. Niethammer, T.R.; Gallik, D.; Chevalier, Y.; Holzgruber, M.; Baur-Melnyk, A.; Müller, P.E.; Pietschmann, M.F. Effect of the defect localization and size on the success of third-generation autologous chondrocyte implantation in the knee joint. Internat. Orthop. 2021, 45, 1483–1491.
  70. Nordberg, R.C.; Otarola, G.A.; Wang, D.; Hu, J.C.; Athanasiou, K.A. Navigating regulatory pathways for translation of biologic cartilage repair products. Sci. Transl. Med. 2022, 14, eabp8163.
  71. Laurent, A.; Hirt-Burri, N.; Scaletta, C.; Michetti, M.; de Buys Roessingh, A.S.; Raffoul, W.; Applegate, L.A. Holistic approach of Swiss fetal progenitor cell banking: Optimizing safe and sustainable substrates for regenerative medicine and biotechnology. Front. Bioeng. Biotechnol. 2020, 8, 557758.
  72. Laurent, A.; Abdel-Sayed, P.; Ducrot, A.; Hirt-Burri, N.; Scaletta, C.; Jaccoud, S.; Nuss, K.; de Buys Roessingh, A.S.; Raffoul, W.; Pioletti, D.P.; et al. Development of standardized fetal progenitor cell therapy for cartilage regenerative medicine: Industrial transposition and preliminary safety in xenogeneic transplantation. Biomolecules 2021, 11, 250.
  73. Abdel-Sayed, P.; Darwiche, S.E.; Kettenberger, U.; Pioletti, D.P. The role of energy dissipation of polymeric scaffolds in the mechanobiological modulation of chondrogenic expression. Biomaterials 2014, 35, 1890–1897.
  74. Nasrollahzadeh, N.; Applegate, L.A.; Pioletti, D.P. Development of an effective cell seeding technique: Simulation, implementation, and analysis of contributing factors. Tissue Eng. Part C 2017, 23, 485–496.
  75. Nasrollahzadeh, N.; Karami, P.; Wang, J.; Bagheri, L.; Guo, Y.; Abdel-Sayed, P.; Laurent-Applegate, L.; Pioletti, D.P. Temperature evolution following joint loading promotes chondrogenesis by synergistic cues via calcium signaling. eLife 2022, 11, e72068.
  76. Studer, D.; Cavalli, E.; Formica, F.A.; Kuhn, G.A.; Salzmann, G.; Mumme, M.; Steinwachs, M.R.; Applegate, L.A.; Maniura-Weber, K.; Zenobi-Wong, M. Human chondroprogenitors in alginate-collagen hybrid scaffolds produce stable cartilage in vivo. J. Tissue Eng. Regen. Med. 2017, 11, 3014–3026.
  77. Cavalli, E.; Fisch, P.; Formica, F.A.; Gareus, R.; Linder, T.; Applegate, L.A.; Zenobi-Wong, M. A comparative study of cartilage engineered constructs in immunocompromised, humanized and immunocompetent mice. J. Immunol. Regen. Med. 2018, 2, 36–46.
  78. Levinson, C.; Lee, M.; Applegate, L.A.; Zenobi-Wong, M. An injectable heparin-conjugated hyaluronan scaffold for local delivery of transforming growth factor β1 promotes successful chondrogenesis. Acta Biomater. 2019, 99, 168–180.
  79. Li, F.; Levinson, C.; Truong, V.X.; Laurent-Applegate, L.A.; Maniura-Weber, K.; Thissen, H.; Forsythe, J.F.; Zenobi-Wong, M.; Frith, J.E. Microencapsulation improves chondrogenesis in vitro and cartilaginous matrix stability in vivo compared to bulk encapsulation. Biomater. Sci. 2020, 8, 1711–1725.
  80. Tosoratti, E.; Fisch, P.; Taylor, S.; Laurent-Applegate, L.A.; Zenobi-Wong, M. 3D-printed reinforcement scaffolds with targeted biodegradation properties for the tissue engineering of articular cartilage. Adv. Healthc. Mat. 2021, 10, e2101094.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Feedback