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

We read with interest the systematic review by Rutgers et al.1 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 themorphologic 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)2 and the Modified Mankin3. 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 score3, 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 death4. However, the common interpretation of the term necrosis (from the Greek n3kró2, “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)5. However, this approach is laborious, and only reflects the late phases of the multistep apoptotic event5. 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 cell4. 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 tissues4. Electron microscopy also may provide a more detailed ultrastructural characterization of apoptotic cells. For in vitro analysis, there are several ways to quantify apoptosis4. 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 cells4. 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.