In this editorial of the first

In this editorial of the first anniversary issue of , we cannot help but reflect on aging. Tremendous biomedical successes over the last century have contributed to ever-increasing life expectancies. In its September 30, 2015 , the World Health Organization estimates that the global average life expectancy is now greater than 60years. In developed nations, 20% of the population is older than 65years. This proportion is expected to grow to 25% by 2050, the same time that the global life expectancy reaches greater than 70years. An increase in lifespan, though, is not necessarily good news. Disease risk exponentially increases with age, with older populations being at greatest risk for cardiovascular disease, cancer, chronic respiratory illness, musculoskeletal diseases, and neurological and cognitive disorders. Already creaking health care systems may be unable to withstand the impending weight of over one billion elderly patients by 2050. The challenge now is not only how to increase lifespan, but also how to increase healthspan — the years one spends subjectively content and without burdensome medical needs.
Musculoskeletal disorders including osteoarthritis (OA) represent a major cause of disability and morbidity, and cause an enormous burden for health and social care systems globally. In the Global Burden of Disease 2010 study, hip and knee OA was ranked as the 11th highest contributor to global disability (), and its prevalence is set to increase in parallel with the number of people aged 60years and older. Articular cartilage within synovial joints has limited self-repair capacity because of its avascular nature and the low proliferation rate of chondrocytes, the main cell type responsible for its maintenance. Chondrocytes reside in a unique aa-dutp of cartilage extracellular matrix (ECM) that consists of collagen type II, large aggregating proteoglycans (e.g. aggrecan), glycosaminoglycans, hyaluronan, other non-collagenous proteins (e.g. COMP), and a large amount of water and mobile cations (i.e. Na, K, Ca); this composition allows cartilage to resist biomechanical forces (). Cell-based therapies are rapidly being developed in a number of diseases including bone and joint disorders. As OA is currently incurable, novel biological and cell-based therapies that can effectively treat joint degeneration are high priorities in regenerative medicine. Multipotent mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue and umbilical cord (UC) show considerable promise for use in cartilage repair. Under appropriate micro-environmental conditions they can proliferate and give rise to chondrocytes and other related mesenchymal cell phenotypes, allowing them to act as key players in regenerating injured tissue following injury and trauma (). Another key feature of MSCs is their capacity to modulate immune responses and , making them well-suited for the treatment of systemic inflammatory and autoimmune conditions that affect synovial joints. Their immunosuppressive nature extends to both the innate and adaptive immune system through interactions with dendritic cells, natural killer cells, macrophages and B and T lymphocytes by means of cell–cell contacts or soluble mediators (). Given the avascular and alymphatic characteristics of articular cartilage and the specific features of the ECM that can shield the MHC molecules from recognition by host cells, an immune response against allogeneic chondrocytes or osteochondral constructs in the host has not been reported. However, the immunomodulatory effects of MSCs may have critical outcomes in diseases of the musculoskeletal system where an inflammatory or autoimmune process is at the core of the main disease. The molecular mechanisms underlying the effects of MSCs on the immune system are diverse and employ the release of soluble factors such as interleukin-10, tumour necrosis factor-alpha, transforming growth factor-beta, prostaglandin-E and indoleamine-2,3-dioxygenase by MSCs. UC-MSCs express the HLA-E, HLA-F and HLA-G non-canonical type I MHC receptors. In addition, the fact that B7-H3 (CD276), a co-stimulatory molecule that inhibits T cell activation, was demonstrated to be expressed not only in undifferentiated UC-MSCs but persisted following differentiation towards the chondrogenic lineage indicate that differentiated UC-MSCs continue to have immunosuppressive characteristics, which is an added advantage with potentially important clinical implications ().