Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc

Abstract

Despite the high prevalence of intervertebral disc disease, little is known about changes in intervertebral disc cells and their regenerative potential with ageing and intervertebral disc degeneration. Here we identify populations of progenitor cells that are Tie2 positive (Tie2+) and disialoganglioside 2 positive (GD2+), in the nucleus pulposus from mice and humans. These cells form spheroid colonies that express type II collagen and aggrecan. They are clonally multipotent and differentiated into mesenchymal lineages and induced reorganization of nucleus pulposus tissue when transplanted into non-obese diabetic/severe combined immunodeficient mice. The frequency of Tie2+ cells in tissues from patients decreases markedly with age and degeneration of the intervertebral disc, suggesting exhaustion of their capacity for regeneration. However, progenitor cells (Tie2+GD2+) can be induced from their precursor cells (Tie2+GD2−) under simple culture conditions. Moreover, angiopoietin-1, a ligand of Tie2, is crucial for the survival of nucleus pulposus cells. Our results offer insights for regenerative therapy and a new diagnostic standard.

FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration

“…Human NP cells were isolated following the protocol described by Sakai et al (2012) and maintained in Dulbecco's modified Eagle's medium (DMEM) containing 10% calf serum (CS) at 37°C in 5% CO 2% and 20% O 2 . Cells with less than three passages were used in all experiments.…”

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

“…More recently, Sakai and colleagues [68] identified a subpopulation of cells within the rat and human NP (characterised by being (Tie2 ? and GD2 ?…”

The Role of Cell Clusters in Intervertebral Disc Degeneration and its Relevance behind Repair

“…Further, nucleus cells also have been shown to be immunopositive to Tie-2, a tyrosine kinase receptor that forms ligand with angiopoietin-1, that maintains the progenitor potential of the cells and protects them from apoptosis [75,76]. Progenitor populations of nucleus pulposus cells have been shown to be multipotent, and are capable of differentiating into adipocytes, osteocytes and chondrocytes [77] but these nucleus pulposus cells do not terminally differentiate as stem cell do, and maintain their phenotype as cartilage cells, a number of intercellular signalling mechanism is shown to be upregulated during proliferation and differentation (Table 2), but understanding about these regulators and how they control accurate differentiation of the progenitor cells are still at a preliminary stage of investigation.…”