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

Daisuke Sakai (), Yoshihiko Nakamura, Tomoko Nakai, Taishi Mishima, Shunichi Kato, Sibylle Grad, Mauro Alini, Makarand V. Risbud, Danny Chan, Kathryn S.E. Cheah, Ken-ichi Yamamura, Koichi Masuda, Hideyuki Okano, Kiyoshi Ando and Joji Mochida
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Daisuke Sakai: Surgical Science, Tokai University School of Medicine
Yoshihiko Nakamura: Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine
Tomoko Nakai: Surgical Science, Tokai University School of Medicine
Taishi Mishima: Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine
Shunichi Kato: Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine
Sibylle Grad: AO Research Institute
Mauro Alini: AO Research Institute
Makarand V. Risbud: Thomas Jefferson University College of Medicine
Danny Chan: The University of Hong Kong
Kathryn S.E. Cheah: The University of Hong Kong
Ken-ichi Yamamura: Institute of Molecular Embryology and Genetics, Kumamoto University
Koichi Masuda: University of California
Hideyuki Okano: Keio University School of Medicine
Kiyoshi Ando: Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine
Joji Mochida: Surgical Science, Tokai University School of Medicine

Nature Communications, 2012, vol. 3, issue 1, 1-11

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms2226

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