The potential role of mesenchymal stem cell therapy for intervertebral disc degeneration: a critical overview

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Low-back pain is the most common health problem for men and women between 20 and 50 years of age, resulting in 13 million doctor visits in the US annually, with significant costs to society in terms of lost time from work and direct and indirect medical expenses. Although the exact origin of most cases of low-back pain remains unknown, it is understood that degenerative damage to the intervertebral disc (IVD) plays a central role in the pathogenic mechanism leading to this disorder. Current treatment modalities for disc-related back pain (selective nerve root blocks, surgical discectomy and fusion) are costly procedures aimed only at alleviating symptoms. Consequently, there is growing interest in the development of novel technologies to repair or regenerate the degenerated IVD. Recently, mesenchymal stem cells (MSCs) have been found to possess the capacity to differentiate into nucleus pulposus–like cells capable of synthesizing a physiological, proteoglycan-rich extracellular matrix characteristic of healthy IVDs. In this article, the authors review the use of MSCs for repopulation of the degenerating IVD. Although important obstacles to the survival and proliferation of stem cells within the degenerating disc need to be overcome, the potential for MSC therapy to slow or reverse the degenerative process remains substantial.

Abbreviations used in this paper:CD = cluster of differentiation; ECM = extracellular matrix; IL = interleukin; IVD = intervertebral disc; MSC = mesenchymal stem cell; NP = nucleus pulposus; TGFβ = transforming growth factor–β; 3D = three-dimensional.

Low-back pain is the most common health problem for men and women between 20 and 50 years of age, resulting in 13 million doctor visits in the US annually, with significant costs to society in terms of lost time from work and direct and indirect medical expenses. Although the exact origin of most cases of low-back pain remains unknown, it is understood that degenerative damage to the intervertebral disc (IVD) plays a central role in the pathogenic mechanism leading to this disorder. Current treatment modalities for disc-related back pain (selective nerve root blocks, surgical discectomy and fusion) are costly procedures aimed only at alleviating symptoms. Consequently, there is growing interest in the development of novel technologies to repair or regenerate the degenerated IVD. Recently, mesenchymal stem cells (MSCs) have been found to possess the capacity to differentiate into nucleus pulposus–like cells capable of synthesizing a physiological, proteoglycan-rich extracellular matrix characteristic of healthy IVDs. In this article, the authors review the use of MSCs for repopulation of the degenerating IVD. Although important obstacles to the survival and proliferation of stem cells within the degenerating disc need to be overcome, the potential for MSC therapy to slow or reverse the degenerative process remains substantial.

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Address reprint requests to: Frank L. Acosta Jr., M.D., Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, M-779, Box 0112, San Francisco, California 94143-0112. email: acostaf@neurosurg.ucsf.edu.

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