Anti-COL2A1 monoclonal antibody, clone COLL-II

Collagens and elastin are 'building blocks' of tissues and extracellular matrix. Mutations in these proteins cause severe congenital syndromes. Adverse genetic variations may accelerate the aging process in adults contributing to premature morbidity, disability and/or mortality. Favorable variants may contribute to longevity and/or healthy aging, but this is much less studied. We reviewed the association between variation in the genes of collagens and elastin and premature aging, accelerated aging, age-related diseases and/or frailty; and the association between genetic variation in those and longevity and/or healthy aging in humans. A systematic search was conducted in MEDLINE and other online databases (OMIM, Genetics Home Reference, Orphanet, ClinVar). Results suggest that genetic variants lead to aging phenotypes of known congenital disease, but also to association with common age-related diseases in adults without known congenital disease. This may be due to the variable penetrance and expressivity of many variants. Some collagen variants have been associated with longevity or healthy aging. A limitation is that most studies had < 1000 participants and their criterion for statistical significance was p < 0.05. Results highlight the importance of adopting a lifecourse approach to the study of the genomics of aging. Gerontology can help with new methodologies that operationalize biological aging.

Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-beta 3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.