Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage

Abstract

We read with interest the systematic review by Rutgers et al.1Rutgers M. van Pelt M.J. Dhert W.J. Creemers L.B. Saris D.B. Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage.Osteoarthritis Cartilage. 2010; 18: 12-23Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar on the evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage. The authors should be congratulated for their efforts. However, in general, we find that one of the major problems of histopathological interpretation of cartilage is the morphologic evaluation of cell viability. In table IV of the article in question, 2 scores are reported to evaluate cell viability: the International Cartilage Repair Society (ICRS)2Mainil-Varlet P. Aigner T. Brittberg M. Bullough P. Hollander A. Hunziker E. et al.Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS).J Bone Joint Surg Am. 2003; 85-A: 45-57PubMed Google Scholar and the Modified Mankin3Uhl M. Lahm A. Bley T.A. Haberstroh J. Mrosek E. Ghanem N. et al.Experimental autologous osteochondral plug transfer in the treatment of focal chondral defects: magnetic resonance imaging signs of technical success in sheep.Acta Radiol. 2005; 46: 875-880Crossref PubMed Scopus (12) Google Scholar. In the original manuscript describing the ICRS score, no clarification on the methodology to be used to evaluate cell viability on histopathological specimens was provided. The only information regarding the cell population viability was the classification into predominantly viable, partially viable, <10% viable. In the original manuscript describing the Modified Mankin score3Uhl M. Lahm A. Bley T.A. Haberstroh J. Mrosek E. Ghanem N. et al.Experimental autologous osteochondral plug transfer in the treatment of focal chondral defects: magnetic resonance imaging signs of technical success in sheep.Acta Radiol. 2005; 46: 875-880Crossref PubMed Scopus (12) Google Scholar, the authors never used the word “viability”. They used the term quality of cartilage (necrotic, fibrous, hyaline). Necrosis and viability are definitely two different entities. Strictly speaking, necrosis encompasses all forms of programmed and non-programmed cell death4Aigner T. Kim H.A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.Arthritis Rheum. 2002; 46: 1986-1996Crossref PubMed Scopus (155) Google Scholar. However, the common interpretation of the term necrosis (from the Greek νɛκρóς, “dead”) is the non-programmed death of cells, in contrast to apoptosis, which is a “programmed” cell death. Histopathological features of apoptotic cell death include the classic fragmented nuclei (apoptotic bodies)5Pritzker K.P. Gay S. Jimenez S.A. Ostergaard K. Pelletier J.P. Revell P.A. et al.Osteoarthritis cartilage histopathology: grading and staging.Osteoarthritis Cartilage. 2006; 14: 13-29Abstract Full Text Full Text PDF PubMed Scopus (1225) Google Scholar. However, this approach is laborious, and only reflects the late phases of the multistep apoptotic event5Pritzker K.P. Gay S. Jimenez S.A. Ostergaard K. Pelletier J.P. Revell P.A. et al.Osteoarthritis cartilage histopathology: grading and staging.Osteoarthritis Cartilage. 2006; 14: 13-29Abstract Full Text Full Text PDF PubMed Scopus (1225) Google Scholar. Theoretically, it cannot be excluded that cell death may occur after cell division, resulting in cartilage lacunae containing cell debris, together with only one viable cell4Aigner T. Kim H.A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.Arthritis Rheum. 2002; 46: 1986-1996Crossref PubMed Scopus (155) Google Scholar. For these reasons, several different techniques have been developed to identify apoptotic cell death at earlier stages, including in situ end-labeling or TUNEL technologies to detect DNA strand breaks within tissues4Aigner T. Kim H.A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.Arthritis Rheum. 2002; 46: 1986-1996Crossref PubMed Scopus (155) Google Scholar. Electron microscopy also may provide a more detailed ultrastructural characterization of apoptotic cells. For in vitro analysis, there are several ways to quantify apoptosis4Aigner T. Kim H.A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.Arthritis Rheum. 2002; 46: 1986-1996Crossref PubMed Scopus (155) Google Scholar. In conclusion, detection of apoptotic bodies is too restrictive, and, although electron microscopy appears to be the gold standard, it is complicated, and does not allow the investigation of large numbers of samples or cells4Aigner T. Kim H.A. Apoptosis and cellular vitality: issues in osteoarthritic cartilage degeneration.Arthritis Rheum. 2002; 46: 1986-1996Crossref PubMed Scopus (155) Google Scholar. With common histopathological staining, evaluation of cell viability may lead to diagnostic errors. Given the above considerations, we therefore question whether it is practical to include the variable cell viability in the currently used histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage. None.