The definition of quality controls for cell therapy and engineered product manufacturing processes is critical for safe, effective, and standardized clinical implementation. Using the example context of cartilage grafts engineered from autologous nasal chondrocytes, currently used for articular cartilage repair in a phase II clinical trial, we outlined how gene expression patterns and generalized linear models can be introduced to define molecular signatures of identity, purity, and potency. We first verified that cells from the biopsied nasal cartilage can be contaminated by cells from a neighboring tissue, namely perichondrial cells, and discovered that they cannot deposit cartilaginous matrix. Differential analysis of gene expression enabled the definition of identity markers for the two cell populations, which were predictive of purity in mixed cultures. Specific patterns of expression of the same genes were significantly correlated with cell potency, defined as the capacity to generate tissues with histological and biochemical features of hyaline cartilage. The outlined approach can now be considered for implementation in a good manufacturing practice setting, and offers a paradigm for other regenerative cellular therapies.

We report on a patient who at 61 years of age presented with two nodular melanomas in the right nasal cavity. These tumors were limited to the mucosal membrane and were accompanied by a large amount of atypical hyperplasia of the melanocytes within the glandular and surface epithelium of various other samples of the mucous membrane, a finding also verified immunohistochemically. These tumors were treated surgically. In the clinical course, after a prolonged tumor-free interval, a malignant melanoma of the contralateral nasal cavity occurred, in addition to recurrences in the area of the primary tumor. It seems likely that the large, diffuse proliferation of atypical melanocytes observed could have been the starting point of both the tumor recurrences and the second primary. Thus, in a histologically proven melanoma in the mucous membranes of the upper respiratory system, a more intense preoperative histological diagnostic procedure, in given cases with the assistance of immunohistochemical methods, could be useful to demonstrate intraepithelial atypical melanocytes. It is possible that by doing this the present poor prognosis for mucosal melanomas of the upper respiratory tract might be improved.

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