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

被引：428

作者：

Sakai, Daisuke ^{[1
,2
,3
]}

Nakamura, Yoshihiko ^{[2
]}

Nakai, Tomoko ^{[1
,2
]}

Mishima, Taishi ^{[2
]}

Kato, Shunichi ^{[2
]}

Grad, Sibylle ^{[4
]}

Alini, Mauro ^{[4
]}

Risbud, Makarand V. ^{[5
,6
]}

Chan, Danny ^{[7
]}

Cheah, Kathryn S. E. ^{[7
]}

Yamamura, Ken-ichi ^{[8
]}

Masuda, Koichi ^{[9
]}

Okano, Hideyuki ^{[10
]}

Ando, Kiyoshi ^{[2
,3
]}

Mochida, Joji ^{[1
,2
,3
]}

机构：

[1] Tokai Univ, Sch Med, Dept Orthopaed Surg, Isehara, Kanagawa 2591193, Japan

[2] Tokai Univ, Sch Med, Res Ctr Regenerat Med & Canc Stem Cell, Isehara, Kanagawa 2591193, Japan

[3] Tokai Univ, Inst Med Sci, Isehara, Kanagawa 2591193, Japan

[4] AO Res Inst, CH-7270 Davos, Switzerland

[5] Thomas Jefferson Univ, Coll Med, Dept Orthopaed Surg, Philadelphia, PA 19107 USA

[6] Thomas Jefferson Univ, Coll Med, Grad Program Tissue Engn & Regenerat Med, Philadelphia, PA 19107 USA

[7] Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China

[8] Kumamoto Univ, Div Dev Genet, Inst Mol Embryol & Genet, Kumamoto 8600811, Japan

[9] Univ Calif San Diego, Dept Orthopaed Surg, La Jolla, CA 90293 USA

[10] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

关键词：

MESENCHYMAL STEM-CELLS; NEURAL GANGLIOSIDE GD2; ANULUS FIBROSUS; STROMAL CELLS; GROWTH; DIFFERENTIATION; IDENTIFICATION; COLONIES; THERAPY; SYSTEM;

D O I：

10.1038/ncomms2226

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：11

共 36 条

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