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Intervertebral disc degeneration is one of the major causes of lower back pain for which the common therapeutic interventions are not efficient. A search for alternative therapies for lower back pain and intervertebral disc degeneration includes cell-based therapies. Unfortunately, intervertebral disc degeneration is avascular and thus a hostile environment for cell survival. Furthermore, cellular characterization in intervertebral disc degeneration, and particularly in the nucleus pulposus, is controversial, mainly due to lack of specific markers and species variability. This book adds to the knowledge on cellular and molecular therapies for intervertebral disc degeneration and associated lower back pain. Key Selling Features: Describes the ontogeny and phenotype of intervertebral disc cells Reviews the role that inflammation plays in disco-genic pain Highlights the types of cells that might be used as sources for treating degenerating intervertebral discs Summarizes current alternative therapies Explores methods for cell delivery into degenerated intervertebral discs
Disorders related to the intervertebral disc (IVD) are common causes of morbidity and of severe life quality deterioration. IVD degeneration, although in many cases asymptomatic, is often the origin of painful neck and back diseases. In Western societies IVD related pain and disability account for enormous health care costs as a result of work absenteeism and thus lost production, disability benefits, medical and insurance expenses. Although only a small percentage of patients with disc disorders finally will undergo surgery, spinal surgery has been one of the fastest growing disciplines in the musculoskeletal field in recent years. Nevertheless, current treatment options are still a matter of controversial discussion. In particular, they hardly can restore normal spine biomechanics and prevent degeneration of adjacent tissues. While degeneration affects all areas of the IVD, the most constant and noticeable changes occur in the gel-like central part, the nucleus pulposus (NP). Recent emphasis has therefore been put in biological ways to regenerate the NP; however, there are a number of obstacles to overcome, considering the exceptional biological and biomechanical environment of this tissue. Different biological approaches such as molecular, gene, and cell based therapies have been investigated and have shown promising results in both in vitro and in vivo studies. Nonetheless, considerable hurdles still exist in their application for IVD regeneration in human patients. The choice of the cells and the choice of the cell carrier suitable for implantation pose major challenges for research and development activities. This lecture recapitulates the basics of IVD structure, function, and degeneration mechanisms. The first part reviews the recent progress in the field of disc and stem cell based regenerative approaches. In the second part, most appropriate biomaterials that have been evaluated as cell or molecule carrier to cope with degenerative disc disease are outlined. The potential and limitations of cell- and biomaterial-based treatment strategies and perspectives for future clinical applications are discussed. Table of Contents: Cell Therapy for Nucleus Pulposus Regeneration / Recent Advances in Biomaterial Based Tissue Engineering for Intervertebral Disc Regeneration
Disorders related to the intervertebral disc (IVD) are common causes of morbidity and of severe life quality deterioration. IVD degeneration, although in many cases asymptomatic, is often the origin of painful neck and back diseases. In Western societies IVD related pain and disability account for enormous health care costs as a result of work absenteeism and thus lost production, disability benefits, medical and insurance expenses. Although only a small percentage of patients with disc disorders finally will undergo surgery, spinal surgery has been one of the fastest growing disciplines in the musculoskeletal field in recent years. Nevertheless, current treatment options are still a matter of controversial discussion. In particular, they hardly can restore normal spine biomechanics and prevent degeneration of adjacent tissues. While degeneration affects all areas of the IVD, the most constant and noticeable changes occur in the gel-like central part, the nucleus pulposus (NP). Recent emphasis has therefore been put in biological ways to regenerate the NP; however, there are a number of obstacles to overcome, considering the exceptional biological and biomechanical environment of this tissue. Different biological approaches such as molecular, gene, and cell based therapies have been investigated and have shown promising results in both in vitro and in vivo studies. Nonetheless, considerable hurdles still exist in their application for IVD regeneration in human patients. The choice of the cells and the choice of the cell carrier suitable for implantation pose major challenges for research and development activities. This lecture recapitulates the basics of IVD structure, function, and degeneration mechanisms. The first part reviews the recent progress in the field of disc and stem cell based regenerative approaches. In the second part, most appropriate biomaterials that have been evaluated as cell or molecule carrier to cope with degenerative disc disease are outlined. The potential and limitations of cell- and biomaterial-based treatment strategies and perspectives for future clinical applications are discussed. Table of Contents: Cell Therapy for Nucleus Pulposus Regeneration / Recent Advances in Biomaterial Based Tissue Engineering for Intervertebral Disc Regeneration
This dissertation, "Intervertebral Disc Regeneration Using Mesenchymal Stem Cells: a Mouse Model Study" by 楊帆, Fan, Yang, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Intervertebral disc regeneration using mesenchymal stem cells ─A mouse model study" Submitted by Fan Yang For the degree of Doctor of philosophy At the University of Hong Kong in August, 2007 Degenerative disc disease (DDD) is a common disease which affects millions of people. The causes of DDD include genetics, injury and smoking; however the underlying pathogenesis of this disease is still not very clear. Lack of the suitable animal models which can truly simulate human DDD is part of the difficulties to study the mechanism of disc degeneration. The biological therapies of DDD include protein therapy, gene therapy and cellular therapy. Compared with other traditional therapeutics, stem cell therapy is a potential regenerative method which could replace the dysfunctional disc cells and restore the function of the intervertebral discs. Some previous studies using large animals have shown that the autologous bone marrow derived mesenchymal stem cells (BMSC) could be beneficial to the degenerated disc. But the mechanism of this regeneration is still largely unknown. The scanty of molecular tools and markers hindered the research in this area. Therefore, the objective of this project is to investigate whether BMSC could be beneficial to the murine degenerative intervertebral discs. If the regenerative effect was obtained, the molecular mechanism of regeneration will be dissected using available molecular tools. In order to attain this purpose we firstly established a simple mouse tail model of DDD using a puncturing method. The caudal murine discs were punctured with 31G needle under the microscopic guidance. Disc height analysis and histology confirmed the induced degeneration was successful and progressive degenerative process was observed from 1 to 12 weeks after the puncture. The expression of Col2a1, aggrecan and Sox 9 of the whole disc decreased continuously; Col1a1 increased from 1 to 6 weeks and decreased at 12 weeks. All these data supported that this murine model had some similarities with human DDD and could be used for the evaluation of the effect of BMSC. In the next step we injected allogenic BMSC isolated from green fluorescent protein (GFP) mouse into the degenerated murine discs. The histology and the x-ray analysis showed that the injury induced degenerative process was delayed from 4 to 24 weeks after the injection of the BMSC. The expression of Col2a1, aggrecan and Sox9 increased in the regenerated disc. Type II collagen increased continuously in the regenerated nucleus pulposus. The number of GFP positive cells which express Col2a1 increased during this regeneration process, suggesting that the chondrocytic differentiation of BMSC was involved in this regeneration process. The increased expression of Col2a1 by differentiated stem cells contributes to the regeneration of the intervertebral disc. In conclusion, a simple mouse model of DDD was established to evaluate the therapeutic effect of BMSC. It was promising to observe that the progressive degeneration was delayed by the injected stem cells. The in vivo chondrocytic differentiation of the BMSC contributes to this structural restoration of the intervertebral discs. The results of this project provided further evidence that in vivo differentiation of the stem cells is an important aspect of the regenerative mechanisms. DOI: 10.5353/th_b3955697 Subjects: Interve
The intervertebral disc is a complex structure that separates opposing vertebrae, permits a wide range of motion, and accommodates high biomechanical forces. Disc degeneration leads to a loss of function and is often associated with excruciating pain. Written by leading scientists and clinicians, the first part of the book provides a review of the basic biology of the disc in health and disease. The second part considers strategies to mitigate the effects of disc degeneration and discusses the possibility of engineering replacement tissues. The final section is devoted to approaches to model normal development and elucidate the pathogenesis of degenerative disc disease using animal, organ and cell culture techniques. The book bridges the gap between the basic and clinical sciences; the target audience includes basic scientists, orthopaedists and neurologists, while at the same time appealing to the needs of graduate students, medical students, interns and fellows.
Low back pain is a common disorder in the clinical treatment of the Department of Orthopedics. Lumbar intervertebral disc degeneration is a main reason for the chronic pain and the process is difficult to reverse. Traditional treatment methods include conservative treatment and surgical treatment. Although the clinical symptoms caused by intervertebral disc degeneration can be alleviated to a certain extent, these treatment methods do not solve the fundamental issues and they also produce corresponding complications. The rise of tissue engineering technology and its applications in different fields have brought new ideas for the treatment of intervertebral disc degeneration. This book discusses the fundamentals as well as more recent developments in stem cell therapy and tissue engineering technology and offers an alternative for treating degeneration of intervertebral discs.
Potential Gene Therapy for Intervertebral Disc Degeneration.
Healthcare decision makers in search of reliable information that compares health interventions increasingly turn to systematic reviews for the best summary of the evidence. Systematic reviews identify, select, assess, and synthesize the findings of similar but separate studies, and can help clarify what is known and not known about the potential benefits and harms of drugs, devices, and other healthcare services. Systematic reviews can be helpful for clinicians who want to integrate research findings into their daily practices, for patients to make well-informed choices about their own care, for professional medical societies and other organizations that develop clinical practice guidelines. Too often systematic reviews are of uncertain or poor quality. There are no universally accepted standards for developing systematic reviews leading to variability in how conflicts of interest and biases are handled, how evidence is appraised, and the overall scientific rigor of the process. In Finding What Works in Health Care the Institute of Medicine (IOM) recommends 21 standards for developing high-quality systematic reviews of comparative effectiveness research. The standards address the entire systematic review process from the initial steps of formulating the topic and building the review team to producing a detailed final report that synthesizes what the evidence shows and where knowledge gaps remain. Finding What Works in Health Care also proposes a framework for improving the quality of the science underpinning systematic reviews. This book will serve as a vital resource for both sponsors and producers of systematic reviews of comparative effectiveness research.
This book provides a brief snapshot of recent research on the subject of intervertebral disc degeneration and how this specific organ could be regenerated. It provides stimuli to the reader in representing research from different angles in this cross-disciplinary field of spine surgeons, mechanical engineers and biologists. In particular, it is instructive as to how disc herniations could be successfully induced in vitro and, also, to how novel cell-based therapies using rare autochthonous stem cells could potentially be used in the future.
Tightly linked to tissue engineering and regenerative medicine, genetic and cellular therapies have drawn universal attention. Since genetic sequencing is critical for precision medicine, the combination of bioinformatics and therapies is important to conduct prescriptive and predictive analytics based on genetic sequencing data. Bioinformatics and computational approaches have been widely considered for the development of genetic and cellular therapies. Therefore, the current research topic aims to cover recent advances in studies such as functional genomics, proteomics, metabolomics, and bioinformatics that bring in new perspectives on genetic therapies. The central goal of regenerative medicine is to replace damaged or diseased tissue with cells that are integrated and functioning optimally. Stem cell-based therapy is restricted by the limited availability of cell sources, the excessive cost, and the anticipated difficulties of clinical translation and ethical approval. Some promising alternatives are to incite the patient's innate ability of tissue repairs such as in situ tissue regeneration, which has the potential to provide new therapeutic options for tissue engineering and regenerative medicine. These innovative cellular therapies are also contained in our research topic.