Abstract
Tissue engineering products (TEP) are a new type of medicines resulting from the combination of cells, scaffolds, and/or signalling factors, which can be used for the regeneration of damaged tissues thus opening new avenues for the treatment of complex conditions. However, such combination of biologically active elements, particularly living cells, poses an unprecedented challenge for their production under pharmaceutical standards.
In the methods presented here, we formulated two types of TEP based on the use of multipotent mesenchymal stromal cells with osteogenic potential combined with osteoinductive and osteoconductive bony particles from tissue bank embedded in a fibrin hydrogel that, altogether, can induce the generation of new tissue while adapting to the diverse architecture of bony defects. In agreement with pharmaceutical quality and regulatory requirements, procedures presented herein can be performed in compliance with current good manufacturing practices and be readily implemented in straightforward facilities at hospitals and academic institutions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Fischbach MA, Bluestone JA, Lim WA (2013) Cell-based therapeutics: the next pillar of medicine. Sci Transl Med 5(179):179ps177. 5/179/179ps7 [pii]. https://doi.org/10.1126/scitranslmed.3005568
Cuende N, Rasko JEJ, Koh MBC, Dominici M, Ikonomou L (2018) Cell, tissue and gene products with marketing authorization in 2018 worldwide. Cytotherapy. S1465-3249(18)30619-4 [pii]. https://doi.org/10.1016/j.jcyt.2018.09.010
Shukla V, Seoane-Vazquez E, Fawaz S, Brown L, Rodriguez-Monguio R (2019) The landscape of cellular and gene therapy products: authorization, discontinuations, and cost. Hum Gene Ther Clin Dev 30(3):102–113. https://doi.org/10.1089/humc.2018.201
Committee for Advanced Therapies (CAT), Schneider CK, Salmikangas P, Jilma B, Flamion B, Todorova LR, Paphitou A, Haunerova I, Maimets T, Trouvin JH, Flory E, Tsiftsoglou A, Sarkadi B, Gudmundsson K, O’Donovan M, Migliaccio G, Ancans J, Maciulaitis R, Robert JL, Samuel A, Ovelgonne JH, Hystad M, Fal AM, Lima BS, Moraru AS, Turcani P, Zorec R, Ruiz S, Akerblom L, Narayanan G, Kent A, Bignami F, Dickson JG, Niederwieser D, Figuerola-Santos MA, Reischl IG, Beuneu C, Georgiev R, Vassiliou M, Pychova A, Clausen M, Methuen T, Lucas S, Schussler-Lenz M, Kokkas V, Buzas Z, Mac Aleenan N, Galli MC, Line A, Gulbinovic J, Berchem G, Fraczek M, Menezes-Ferreira M, Vilceanu N, Hrubisko M, Marinko P, Timon M, Cheng W, Crosbie GA, Meade N, di Paola ML, Vanden Driessche T, Ljungman P, D’Apote L, Oliver-Diaz O, Buttel I, Celis P (2010) Challenges with advanced therapy medicinal products and how to meet them. Nat Rev Drug Discov 9(3):195–201. https://doi.org/10.1038/nrd3052
Vives J, Oliver-Vila I, Pla A (2015) Quality compliance in the shift from cell transplantation to cell therapy in non-pharma environments. Cytotherapy 17(8):1009–1014. https://doi.org/10.1016/j.jcyt.2015.02.002
Soler R, Orozco L, Munar A, Huguet M, López R, Vives J, Coll R, Codinach M, Garcia-Lopez J (2016) Final results of a phase I-II trial using ex vivo expanded autologous Mesenchymal stromal cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee 23(4):647–654. https://doi.org/10.1016/j.knee.2015.08.013
Codinach M, Blanco M, Ortega I, Lloret M, Reales L, Coca MI, Torrents S, Doral M, Oliver-Vila I, Requena-Montero M, Vives J, Garcia-Lopez J (2016) Design and validation of a consistent and reproducible manufacture process for the production of clinical-grade bone marrow-derived multipotent mesenchymal stromal cells. Cytotherapy 18(9):1197–1208. S1465-3249(16)30400-5 [pii]. https://doi.org/10.1016/j.jcyt.2016.05.012
Prat S, Gallardo-Villares S, Vives M, Carreño A, Caminal M, Oliver-Vila I, Chaverri D, Blanco M, Codinach M, Huguet P, Ramírez J, Pinto JA, Aguirre M, Coll R, Garcia-López J, Granell-Escobar F, Vives J (2018) Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis. J Tissue Eng Regen Med 12(1):e532–e540. https://doi.org/10.1002/term.2323
Bieback K, Kuçi S, Schäfer R (2019) Production and quality testing of multipotent mesenchymal stromal cell therapeutics for clinical use. Transfusion. https://doi.org/10.1111/trf.15252
Galipeau J, Sensebe L (2018) Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell 22(6):824–833. S1934-5909(18)30222-4 [pii]. https://doi.org/10.1016/j.stem.2018.05.004
Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ, Canadian Critical Care Trials Group (2012) Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One 7(10):e47559. https://doi.org/10.1371/journal.pone.0047559
Oliver-Vila I, Coca MI, Grau-Vorster M, Pujals-Fonts N, Caminal M, Casamayor-Genescà A, Ortega I, Reales L, Pla A, Blanco M, García J, Vives J (2016) Evaluation of a cell-banking strategy for the production of clinical grade mesenchymal stromal cells from Wharton's jelly. Cytotherapy 18(1):25–35. https://doi.org/10.1016/j.jcyt.2015.10.001
Grau-Vorster M, Rodriguez L, Del Mazo-Barbara A, Mirabel C, Blanco M, Codinach M, Gomez SG, Querol S, Garcia-Lopez J, Vives J (2019) Compliance with good manufacturing practice in the assessment of immunomodulation potential of clinical grade multipotent mesenchymal stromal cells derived from Wharton’s Jelly. Cell 8(5). https://doi.org/10.3390/cells8050484
Mirabel C, Puente-Massaguer E, Del Mazo-Barbara A, Reyes B, Morton P, Gòdia F, Vives J (2018) Stability enhancement of clinical grade multipotent mesenchymal stromal cell-based products. J Transl Med 16(1):291. https://doi.org/10.1186/s12967-018-1659-4
Caminal M, Velez R, Rabanal RM, Vivas D, Batlle-Morera L, Aguirre M, Barquinero J, Garcia J, Vives J (2017) A reproducible method for the isolation and expansion of ovine mesenchymal stromal cells from bone marrow for use in regenerative medicine preclinical studies. J Tissue Eng Regen Med 11(12):3408–3416. https://doi.org/10.1002/term.2254
Velez R, Hernandez-Fernandez A, Caminal M, Vives J, Soldado F, Fernandez A, Pla A, Aguirre M (2012) Treatment of femoral head osteonecrosis with advanced cell therapy in sheep. Arch Orthop Trauma Surg 132(11):1611–1618. https://doi.org/10.1007/s00402-012-1584-6
Del Mazo-Barbara A, Nieto V, Mirabel C, Reyes B, Garcia-Lopez J, Oliver-Vila I, Vives J (2016) Streamlining the qualification of computerized systems in GxP-compliant academic cell therapy facilities. Cytotherapy. S1465-3249(16)30414-5 [pii]. https://doi.org/10.1016/j.jcyt.2016.06.003
Acknowledgments
The authors would like to acknowledge former members of Xcelia and current members of Servei de Teràpia Cel·lular for technical support and advice. Our laboratory is member of the Spanish Cell Therapy Network (TerCel, RD16/0011/0028) and awarded by the Generalitat de Catalunya as Consolidated Research Group (2017SGR719). Our work is developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund) 2014–2020. Project PI19/01788 is funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF) – A way to build Europe.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media New York
About this protocol
Cite this protocol
Vives, J., Rodríguez, L., Coca, M.I., Reales, L., Cabrera-Pérez, R., Martorell, L. (2020). Use of Multipotent Mesenchymal Stromal Cells, Fibrin, and Scaffolds in the Production of Clinical Grade Bone Tissue Engineering Products. In: Turksen, K. (eds) Stem Cells and Good Manufacturing Practices. Methods in Molecular Biology, vol 2286. Humana, New York, NY. https://doi.org/10.1007/7651_2020_280
Download citation
DOI: https://doi.org/10.1007/7651_2020_280
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1326-9
Online ISBN: 978-1-0716-1327-6
eBook Packages: Springer Protocols