Title

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

Authors

Daisuke Sakai, Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine; Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine; Institute of Medical Sciences, Tokai University
Yoshihiko Nakamura, Research Center for Regenerative Medicine and Cancer Stem Cell
Tomoko Nakai, Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine; Research Center for Regenerative Medicine and Cancer Stem Cell, 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
Makarand V Risbud, Department of Orthopaedic Surgery and Graduate, Program in Tissue Engineering and Regenerative Medicine, Thomas Jefferson University College of MedicineFollow
Danny Chan, Department of Biochemistry, University of Hong Kong
Kathryn S E Cheah, Department of Biochemistry, University of Hong Kong
Ken-ichi Yamamura, Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University
Koichi Masuda, Department of Orthopaedic Surgery, University of California, San Diego
Hideyuki Okano, Department of Physiology, Keio University School of Medicine
Kiyoshi Ando, Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine; Institute of Medical Sciences, Tokai University
Joji Mochida, Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine; Research Center for Regenerative Medicine and Cancer Stem Cell, Tokai University School of Medicine; Institute of Medical Sciences, Tokai University
Mauro Alini, AO Research Institute

Document Type

Article

Publication Date

12-11-2012

Comments

This article has been peer reviewed. It was published in: Nature Communications.

Volume 3, 2012, Article number 1264.

The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535337/. DOI: 10.1038/ncomms2226

Copyright © 2012, Nature Publishing Group, a division of Macmillan Publishers Limited

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.