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

Citations Over TimeTop 1% of 2012 papers

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.

Related Papers

• → The role of proteoglycans in aging, degeneration and repair of the intervertebral disc(2002)216 cited
• → The efficacy of Link N as a mediator of repair in a rabbit model of intervertebral disc degeneration(2011)77 cited
• → Human Intervertebral Disc Cells Promote Nerve Growth Over Substrata of Human Intervertebral Disc Aggrecan(2006)49 cited
• → The effects of human intervertebral disc aggrecan on neuronal and endothelial cell growth(2004)4 cited
• → Injection of a Novel Biomimetic Aggrecan for the Restoration of Intervertebral Disc Tissue Mechanics(2013)