The promise of mesenchymal stem cells for intervertebral disc repair

Abstract

Disc degeneration (DD) is a major musculoskeletal condition affecting 80% of the general global population [1]. The associated low back pain (LBP) has major socioeconomic impact reviewed in [2]. In the past 25 years a number of promising biological therapies have been investigated for the treatment of degenerative Disc Disease (DDD) and these have identified many potential molecular targets for biologic intervention [3-5]. These include agents which induce cellular proliferation, matrix production, regulate matrix metallo protease (MMP) and tissue inhibitor of metallo protease (TIMP) production, inflammation, vascular ingrowth and cell viability [6]. The cell density in the IVD is low [7] and disc cells are exposed to a hostile environment of low oxygen tension, high lactic acid levels, low nutrition and a high hydrostatic pressure leading to cell death and a diminution in cell numbers over time due to cellular senescence [8,9], apoptosis [10,11] and autophagy [12,13]. The resultant decline in cell number with DD places severe demands on any therapeutic measures to alleviate this condition.