Despite the high prevalence of intervertebral disc disease, little is known about changes inintervertebral disc cells and their regenerative potential with ageing and intervertebral discdegeneration. 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 areclonally multipotent and differentiated into mesenchymal lineages and induced reorganizationof nucleus pulposus tissue when transplanted into non-obese diabetic/severe combinedimmunodeficient mice. The frequency of Tie2~+cells in tissues from patients decreasesmarkedly with age and degeneration of the intervertebral disc, suggesting exhaustion of theircapacity for regeneration. However, progenitor cells (Tie2~+GD2~+) can be induced from theirprecursor cells (Tie2~+GD2~-) under simple culture conditions. Moreover, angiopoietin-1, aligand of Tie2, is crucial for the survival of nucleus pulposus cells. Our results offer insights forregenerative therapy and a new diagnostic standard.
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