Mesenchymal Stem Cells Arrest Intervertebral Disc Degeneration Through Chondrocytic Differentiation and Stimulation of Endogenous Cells

被引:122
作者
Yang, Fan [1 ,2 ]
Leung, Victor Y. L. [1 ,3 ]
Luk, Keith D. K. [1 ]
Chan, Danny [3 ]
Cheung, Kenneth M. C. [1 ]
机构
[1] Univ Hong Kong, Dept Orthopaed & Traumatol, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China
[2] Chinese Acad Sci, Shenzhen Inst Adv Technol, Key Lab Biomed Informat & Hlth Engn, Inst Biomed & Hlth Engn, Shenzhen, Peoples R China
[3] Univ Hong Kong, Dept Biochem, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China
关键词
NUCLEUS PULPOSUS CELLS; IN-VITRO; MODEL; REGENERATION; INJURY; TRANSPLANTATION; LIMITATIONS; PHENOTYPE; MOUSE;
D O I
10.1038/mt.2009.146
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest degeneration in rabbit and canine intervertebral discs. In this study, we have used the mouse model to investigate the mechanism of degeneration arrest. BMSC from Egfp transgenic mice were injected into the degenerated murine intervertebral discs induced by annular puncture. We found that BMSC could arrest the progressive degeneration of the discs with significant regeneration of the nucleus pulposus (NP). In the regeneration, expression of proteoglycan genes were upregulated and extracellular matrix (ECM) progressively accumulated in the NP after BMSC injection. Combined in situ hybridization and immunohistochemistry revealed that BMSC underwent chondrocytic differentiation in the regeneration process. Interestingly, BMSC-induced an increase of endogenous notochordal cells in NP and expression of chondrocytic markers. In this study, we have firstly shown that the BMSC could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells.
引用
收藏
页码:1959 / 1966
页数:8
相关论文
共 30 条
[11]   The notochordal cell in the nucleus pulposus: A review in the context of tissue engineering [J].
Hunter, CJ ;
Matyas, JR ;
Duncan, NA .
TISSUE ENGINEERING, 2003, 9 (04) :667-677
[12]   Lumbar disc disorders and low-back pain: Socioeconomic factors and consequences [J].
Katz, JN .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2006, 88A :21-24
[13]   Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease [J].
Lee, Jean-Pyo ;
Jeyakumar, Mylvaganam ;
Gonzalez, Rodolfo ;
Takahashi, Hiroto ;
Lee, Pei-Jen ;
Baek, Rena C. ;
Clark, Dan ;
Rose, Heather ;
Fu, Gerald ;
Clarke, Jonathan ;
McKercher, Scott ;
Meerloo, Jennifer ;
Muller, Franz-Josef ;
Park, Kook In ;
Butters, Terry D. ;
Dwek, Raymond A. ;
Schwartz, Philip ;
Tong, Gang ;
Wenger, David ;
Lipton, Stuart A. ;
Seyfried, Thomas N. ;
Platt, Frances M. ;
Snyder, Evan Y. .
NATURE MEDICINE, 2007, 13 (04) :439-447
[14]   Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction [J].
Leung, Victor Y. L. ;
Chan, Danny ;
Cheung, Kenneth M. C. .
EUROPEAN SPINE JOURNAL, 2006, 15 (Suppl 3) :S406-S413
[15]   Cardiomyocytes can be generated from marrow stromal cells in vitro [J].
Makino, S ;
Fukuda, K ;
Miyoshi, S ;
Konishi, F ;
Kodama, H ;
Pan, J ;
Sano, M ;
Takahashi, T ;
Hori, S ;
Abe, H ;
Hata, J ;
Umezawa, A ;
Ogawa, S .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (05) :697-705
[16]   A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: Correlation between the degree of disc injury and radiological and histological appearances of disc degeneration [J].
Masuda, K ;
Aota, Y ;
Muehleman, C ;
Imai, Y ;
Okuma, M ;
Thonar, EJ ;
Andersson, GB ;
An, HS .
SPINE, 2005, 30 (01) :5-14
[17]  
Nomura T, 2001, CLIN ORTHOP RELAT R, P94
[18]  
Novak A, 2000, GENESIS, V28, P147, DOI 10.1002/1526-968X(200011/12)28:3/4<147::AID-GENE90>3.0.CO
[19]  
2-G
[20]  
Olszewski Waldemar L, 2005, Ann Transplant, V10, P5