Author:
Asnaghi M. Adelaide,Power Laura,Barbero Andrea,Haug Martin,Köppl Ruth,Wendt David,Martin Ivan
Abstract
AbstractThe 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.
Publisher
Cold Spring Harbor Laboratory
Reference61 articles.
1. A functional biological network centered on XRCC3: A new possible marker of chemoradiotherapy resistance in rectal cancer patients;Cancer. Biol. Ther,2015
2. Structural characteristics of septal cartilage and mucoperichondrium
3. Compressive and tensile mechanical properties of the porcine nasal septum;J. Biomech,2014
4. Chondrogenic differentiation of human chondrocytes cultured in the absence of ascorbic acid;J. Tissue Eng. Regen. Med,2018
5. Asnaghi, M.A. , Smith, T. , Martin, I. , Wendt, D. (2014). Bioreactors: enabling technologies for research and manufacturing. In Tissue Engineering, eds. van Blitterswijk, C. , and de Boer, J. (Academic Press/Elsevier, Amsterdam, the Netherlands), 393–426.
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