- Email: [email protected]
Summary statement: biologic repair or regeneration of the intervertebral disc
The Spine Journal 5 (2005) 304S
Summary statement: biologic repair or regeneration of the intervertebral disc D. Greg Anderson, MD, Timothy Yoon, MD, Frank Shen, MD, James Kang, MD, Frank Phillips, MD, Howard An, MD Disc degeneration is a normal part of aging, although the rate and magnitude of degeneration vary widely from individual to individual. Fortunately, most people have few symptoms as a result of the degenerative process. There are, however, a certain proportion of the population who do experience pain and disability due to disc degeneration. Because disc degeneration is observed in essentially all humans, it should not be considered a disease in the same sense as diabetes where the specific underlying pathologic alterations can be defined and measured. Therefore, in this section we will use the term disc degeneration to refer to the degenerative changes of the intervertebral disc. We will use the term symptomatic disc degeneration to refer to a person experiencing pain as the result of the degenerative process in the disc. Over the last quarter century, the underlying cellular and molecular changes that occur during disc degeneration have begun to be elucidated. Degenerative changes begin relatively early in life and progress through a definable sequence of events that result in deterioration of the extracellular matrix leading to diminished biomechanical properties of the disc. Understanding the degenerative process at the molecular level is crucial to the ongoing effort to develop a biologic treatment for disc degeneration that may slow, halt, or reverse the degenerative process for patients with symptoms. Research has identified many potential molecular targets for biologic intervention in the disc. These molecules can be divided into mitogens, which affect cellular division, and cytokines, which are secreted molecules that can affect a wide variety of intercellular processes by binding to cell
1529-9430/05/$ – see front matter doi:10.1016/j.spinee.2005.02.011
쑖 2005 Elsevier Inc. All rights reserved.
surface receptors. At the molecular level, these heterogeneous groups of factors affect a wide variety of cellular processes including inflammation, matrix stability, vascular ingrowth, and cell viability. Molecular factors have therapeutic potential in the treatment of symptomatic degenerative disc disease as a means of achieving tissue repair or symptom reduction. One strategy for symptomatic disc degeneration involves the use of cellular implants to the disc. This approach begins with the harvest of an appropriate cell type. The harvested cells may be expanded in number by in vitro culture and perhaps treated with a molecular agent or gene to enhance the biologic properties of the cell before implantation into the disc. After implantation, it is hoped that the implanted cells will participate directly in tissue repair or may stimulate indigenous cells to produce a larger quantity of extracellular matrix. Gene therapy is another technique for disc repair that is under investigation. In this strategy, a gene or genes encoding biologically active molecule are introduced into the disc, leading to a stimulation of indigenous disc cells to increase the output of matrix constituents. Another form of gene therapy uses cells as a carrier vehicle for genes into the disc. In theory, genes could be used to regulate a variety of processes, including cell division, matrix production, inflammation, and cell death. The future for biologic approaches to disc degeneration appears bright as the molecular basis for disc degeneration and the molecular manipulation of the disc are expanding rapidly. In time, it is reasonable to assume that a viable, clinically applicable biologic repair strategy will be available for this highly prevalent condition.
Summary statement: biologic repair or regeneration of the intervertebral disc D. Greg Anderson, MD, Timothy Yoon, MD, Frank Shen, MD, James Kang, MD, Frank Phillips, MD, Howard An, MD Disc degeneration is a normal part of aging, although the rate and magnitude of degeneration vary widely from individual to individual. Fortunately, most people have few symptoms as a result of the degenerative process. There are, however, a certain proportion of the population who do experience pain and disability due to disc degeneration. Because disc degeneration is observed in essentially all humans, it should not be considered a disease in the same sense as diabetes where the specific underlying pathologic alterations can be defined and measured. Therefore, in this section we will use the term disc degeneration to refer to the degenerative changes of the intervertebral disc. We will use the term symptomatic disc degeneration to refer to a person experiencing pain as the result of the degenerative process in the disc. Over the last quarter century, the underlying cellular and molecular changes that occur during disc degeneration have begun to be elucidated. Degenerative changes begin relatively early in life and progress through a definable sequence of events that result in deterioration of the extracellular matrix leading to diminished biomechanical properties of the disc. Understanding the degenerative process at the molecular level is crucial to the ongoing effort to develop a biologic treatment for disc degeneration that may slow, halt, or reverse the degenerative process for patients with symptoms. Research has identified many potential molecular targets for biologic intervention in the disc. These molecules can be divided into mitogens, which affect cellular division, and cytokines, which are secreted molecules that can affect a wide variety of intercellular processes by binding to cell
1529-9430/05/$ – see front matter doi:10.1016/j.spinee.2005.02.011
쑖 2005 Elsevier Inc. All rights reserved.
surface receptors. At the molecular level, these heterogeneous groups of factors affect a wide variety of cellular processes including inflammation, matrix stability, vascular ingrowth, and cell viability. Molecular factors have therapeutic potential in the treatment of symptomatic degenerative disc disease as a means of achieving tissue repair or symptom reduction. One strategy for symptomatic disc degeneration involves the use of cellular implants to the disc. This approach begins with the harvest of an appropriate cell type. The harvested cells may be expanded in number by in vitro culture and perhaps treated with a molecular agent or gene to enhance the biologic properties of the cell before implantation into the disc. After implantation, it is hoped that the implanted cells will participate directly in tissue repair or may stimulate indigenous cells to produce a larger quantity of extracellular matrix. Gene therapy is another technique for disc repair that is under investigation. In this strategy, a gene or genes encoding biologically active molecule are introduced into the disc, leading to a stimulation of indigenous disc cells to increase the output of matrix constituents. Another form of gene therapy uses cells as a carrier vehicle for genes into the disc. In theory, genes could be used to regulate a variety of processes, including cell division, matrix production, inflammation, and cell death. The future for biologic approaches to disc degeneration appears bright as the molecular basis for disc degeneration and the molecular manipulation of the disc are expanding rapidly. In time, it is reasonable to assume that a viable, clinically applicable biologic repair strategy will be available for this highly prevalent condition.