Abstract
Current developments in tissue engineering strategies for articular cartilage regeneration focus on the design of supportive three-dimensional scaffolds and their use in combination with cells from different sources. The challenge of translating initial successes in small laboratory animals into the clinics involves pilot studies in large animal models, where safety and efficacy should be investigated during prolonged follow-up periods. Here we present, in a single study, the long-term (up to 1 year) effect of biocompatible porous scaffolds non-seeded and seeded with fresh ex vivo expanded autologous progenitor cells that were derived from three different cell sources [cartilage, fat and bone marrow (BM)] in order to evaluate their advantages as cartilage resurfacing agents. An ovine model of critical size osteochondral focal defect was used and the test items were implanted arthroscopically into the knees. Evidence of regeneration of hyaline quality tissue was observed at 6 and 12 months post-treatment with variable success depending on the cell source. Cartilage and BM-derived mesenchymal stromal cells (MSC), but not those derived from fat, resulted in the best quality of new cartilage, as judged qualitatively by magnetic resonance imaging and macroscopic assessment, and by histological quantitative scores. Given the limitations in sourcing cartilage tissue and the risk of donor site morbidity, BM emerges as a preferential source of MSC for novel cartilage resurfacing therapies of osteochondral defects using copolymeric poly-d,l-lactide-co-glycolide scaffolds.
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Acknowledgments
The authors would like to acknowledge Anna Garrit and Cristian de la Fuente for technical assistance; and José Luís Ruiz, Ramón Costa and the crew of the “Servei de Granges i Camps Experimentals” of the Universitat Autònoma de Barcelona (Bellaterra, Spain) for their careful assistance to animal management. This work was supported by “Ministerio de Economía y Competitividad” (Grant Number IPT-300000-2010-0017), “Ministerio de Ciencia e Innovación” (Grant Numbers PSE-010000-2007-4//PSE-010000-2008-4, BIO2008-01985), “Programa de suport a grups d’investigació DGR/DIUE” (Grant number 2009SGR1038) and by the European Regional Development Fund (ERDF), within the National Plan for Scientific Research, Development and Innovation 2008-2011.
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M. Caminal and D. Peris have contributed equally to this work.
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SUPPLEMENTAL Fig. 1. Areas analysed in the histological assessment. “S” corresponds to the superficial zone and “D” for the deep zone. The approximate dimensions are indicated. Superficial cartilage zone: S1, defect site; S2, perilesional area; S3, surrounding native hyaline cartilage. Deep zone: D1, damaged area; D2, adjacent spongy bone. (JPEG 194 kb)
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SUPPLEMENTAL Fig. 2. Necropsy. The only pathological finding in animal F64 was the presence of purulent abscesses in the lung parenchyma (arrow). (JPEG 1605 kb)
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Caminal, M., Peris, D., Fonseca, C. et al. Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage, fat, and bone marrow in an ovine model of osteochondral focal defect. Cytotechnology 68, 907–919 (2016). https://doi.org/10.1007/s10616-015-9842-4
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DOI: https://doi.org/10.1007/s10616-015-9842-4