Intervertebral Disc Regeneration Using Mesenchymal Stem Cells
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Intervertebral Disc Regeneration Using Mesenchymal Stem Cells
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Author : Fan Yang
language : en
Publisher: Open Dissertation Press
Release Date : 2017-01-27
Intervertebral Disc Regeneration Using Mesenchymal Stem Cells written by Fan Yang and has been published by Open Dissertation Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-01-27 with categories.
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
Intervertebral Disc Regeneration Using Mesenchymal Stem Cells
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Author : Fan Yang (Orthopedist.)
language : en
Publisher:
Release Date : 2007
Intervertebral Disc Regeneration Using Mesenchymal Stem Cells written by Fan Yang (Orthopedist.) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with Intervertebral disk categories.
Intervertebral Disc Regeneration By Use Of Autologous Mesenchymal Stem Cells
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Author : Grace Ho
language : en
Publisher: Open Dissertation Press
Release Date : 2017-01-26
Intervertebral Disc Regeneration By Use Of Autologous Mesenchymal Stem Cells written by Grace Ho and has been published by Open Dissertation Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-01-26 with categories.
This dissertation, "Intervertebral Disc Regeneration by Use of Autologous Mesenchymal Stem Cells" by Grace, Ho, 何秀慧, 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 the thesis entitled INTERVERTEBRAL DISC REGENERATION BY USE OF AUTOLOGOUS MESENCHYMAL STEM CELLS submitted by Ho Grace for the degree of Master of Philosophy at the University of Hong Kong in February 2005 Intervertebral disc degeneration is prevalent and is often associated with low back pain and reduced productivity. The etiology of this multi-factorial, age-related disease is not well defined. Disc degeneration is characterized by a reduction in cell density and a decreased in both the proteoglycan and water content. The consequent loss of shock- absorbing capacity results in its structural failure and back pain. The current treatments aim at alleviating the pain symptoms without targeting at the underlying problem. Mesenchymal stem cells (MSCs) are derived from the bone marrow and are capable of self-renewal and differentiation into multiple cell types of different lineages. Because of their unique characteristics, MSCs may be able to repopulate an aging disc population and halt disc degeneration when placed in a local niche that induce the differentiation of MSCs into disc-like cells and secrete disc-like extracellular matrix components. In a pilot study, I demonstrated the persistence of MSCs throughout the three disc compartments (the nucleus pulposus, the annulus fibrosus and the endplate) 12 weeks post-implantation. The MSCs intermingled with endogenous host cells, displaying similar cell morphology and surrounding extracellular matrix composition. To determine the effectiveness of MSCs in treating disc degeneration, a slowly progressive and reproducible animal model of disc degeneration was developed by puncturing the annulus fibrosus percutaneously. By semi-quantitative histological analysis, it was observed that MSCs were able to halt or retard degeneration of the more severely degenerated discs. The data further suggests that the regenerative potential of the MSCs is dependent on the severity of disc degeneration. Radiological analysis suggests that intervertebral disc height, an important consequence of disc degeneration, can be maintained simply by the insertion of a gelatin scaffold, whereas MSCs alone appears to be unable to secrete sufficient matrix to restore this height. Although the collagen-rich scaffold, by itself, was unable to reconstitute the extracellular matrix composition of the disc. Taken together, our experiments suggest that for the best regenerative potential, both cells and scaffold are likely required. An ideal scaffold should allow the restoration of the delicate balance of proteoglycan and collagen content, apart from providing mechanical properties and cell anchorage. Besides demonstrating that the direct MSCs therapy is highly feasible, these observations have profound impact on their application to treat intervertebral disc degeneration in human patients. The timing of stem cell therapy becomes very critical. The degree of the disc degeneration and the type of scaffolds that warrants the best results from the stem cell-based therapy would have to be further investigated. DOI: 10.5353/th_b3154161 Subjects: Stem cells Intervertebral disk - Diseases - Treatment
Cells And Biomaterials For Intervertebral Disc Regeneration
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Author : Sibylle Grad
language : en
Publisher: Springer Nature
Release Date : 2022-06-01
Cells And Biomaterials For Intervertebral Disc Regeneration written by Sibylle Grad and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-06-01 with Science categories.
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
Cells And Biomaterials For Intervertebral Disc Regeneration
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Author : Sibylle Grad
language : en
Publisher: Morgan & Claypool Publishers
Release Date : 2010
Cells And Biomaterials For Intervertebral Disc Regeneration written by Sibylle Grad and has been published by Morgan & Claypool Publishers this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Medical categories.
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
Intervertebral Disc Cell Therapy For Regeneration
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Author : Gwen Crevensten
language : en
Publisher:
Release Date : 2003
Intervertebral Disc Cell Therapy For Regeneration written by Gwen Crevensten and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.
Intervertebral Disc Regeneration By Use Of Autologous Mesenchymal Stem Cells
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Author : Grace Ho
language : en
Publisher:
Release Date : 2005
Intervertebral Disc Regeneration By Use Of Autologous Mesenchymal Stem Cells written by Grace Ho and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005 with Intervertebral disk categories.
Mesenchymal Stem Cells
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Author : Phuc Van Pham
language : en
Publisher: BoD – Books on Demand
Release Date : 2017-11-29
Mesenchymal Stem Cells written by Phuc Van Pham and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-11-29 with Science categories.
Mesenchymal Stem Cells: Isolation, Characterization, and Applications thoroughly presents the isolation, characterization, and some applications of mesenchymal stem cells in the clinic. The book has two parts: "Isolation and Characterization" and "Clinical Perspectives and Applications." In Part I, the subsequent chapters introduce some techniques in isolation, characterization, and purification of mesenchymal stem cells in different tissues. In Part II, some applications of mesenchymal stem cells in the popular diseases, which include cartilage regeneration, spinal cord injury, and osteoarthritis, are discussed. This book provides a succinct yet comprehensive overview of mesenchymal stem cells for advanced students, graduate students, and researchers.
Biological Approaches To Spinal Disc Repair And Regeneration For Clinicians
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Author : Roger Hartl
language : en
Publisher: Thieme
Release Date : 2017-06-30
Biological Approaches To Spinal Disc Repair And Regeneration For Clinicians written by Roger Hartl and has been published by Thieme this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-06-30 with Medical categories.
Top Experts Share Clinical Insights on Biological Interventions for Spine-Related Disease Although there have been significant advancements in minimally invasive spinal surgery techniques in the last few decades, optimal outcomes for chronic low back pain remain elusive. A number of promising clinical trials have been conducted using tissue engineering and biological interventions for disc degeneration. Written by renowned innovators, this is the first book that covers implementation of these groundbreaking approaches for disc disease. The text begins with key fundamentals including anatomy and physiology, pathophysiology, imaging and biomechanics to delineate healthy versus diseased spine. Subsequent sections discuss treatment strategies, research findings, and future developments. Throughout each chapter, renowned spine surgeons and scientists share clinical pearls gleaned from hands-on experience. Key Highlights The current state of the art in biological and tissue engineering procedures for spinal disorders Treatment methodologies including nucleus replacement and repair, annulus fibrosus repair, total disc transplantation, and mechanical total disc replacement Innovative treatment strategies for disc regeneration, such as genes and proteins Growth factors including platelet-rich plasma (PRP), which has shown promise for the stimulation and acceleration of bone and soft tissue healing Cell-based therapy for spinal disc regeneration and repair including the use of stem cells and chondrocytes In-depth discussion of research including animal versus human model, in-vitro, and a summary of biologic clinical trials This is a must-have resource for trainee and practicing orthopaedic surgeons and neurosurgeons who treat patients for spine-related conditions. It is essential reading for all clinicians who have an interest in cutting-edge tissue engineering and biological treatment interventions.
Potential Of Bone Marrow And Umbilical Cord Derived Mesenchymal Stem Cells In Intervertebral Disc Repair
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Author : Fengjuan Lu
language : en
Publisher: Open Dissertation Press
Release Date : 2017-01-26
Potential Of Bone Marrow And Umbilical Cord Derived Mesenchymal Stem Cells In Intervertebral Disc Repair written by Fengjuan Lu and has been published by Open Dissertation Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-01-26 with categories.
This dissertation, "Potential of Bone Marrow and Umbilical Cord Derived Mesenchymal Stem Cells in Intervertebral Disc Repair" by Fengjuan, Lu, 吕凤娟, 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: Introduction: Intervertebral disc (IVD) degeneration is suggested to begin from the nucleus pulposus (NP). Evidence from various studies highlights mesenchymal stem cells (MSC), in most cases using bone marrow derived MSC, as a potential stem cell source for NP regeneration. However MSC can be isolated from many sources with various characteristics. There are indications that fetal or close to fetal tissue sources contain MSC with relatively undifferentiated phenotype with respect to MSC from adult sources. Moreover, umbilical cord (C)-MSC may have better chondrogenic differentiation potential than bone marrow (B)-MSC. We hypothesize CMSC are different from BMSC, and more efficient than BMSC in stimulating NP regeneration. Methods: MSC were isolated from human bone marrow and umbilical cord with corresponding ethical approval. BMSC and CMSC were characterized for cell surface marker expression profile and differentiation potential.. RT-PCR of interest genes in NP cells isolated from scoliosis and degenerate discs was performed to search for NP degeneration indicators. Conditioned media (CM) was collected from confluent MSC monolayer, and used for stimulation of four batches of degenerated NP cells isolated from human degenerative intervertebral discs. Cell proliferation and cytotoxicity were assessed by MTT assay. Proteoglycan content were measured by DMMB assay. Gene expression of a series of degeneration related molecules including ACAN, SOX9, CDH2, CD55, KRT19, KRT18, FBLN1 and MGP, and fibrosis related molecules, including MMP12, HSP47, COL1A1, COL3A1 and FN1, of NP cells in MSC-CM were determined by real- time RT-PCR. All results were normalized to the control cells in basal medium. The expression of discogenic, chondrogenic and osteogenic markers on BMSC and CMSC were compared by RT-PCR. Results and Conclusion: CMSC were similar to BMSC and fulfilled the minimum criteria of MSC, however the expression of CD146, CD106 and Stro-1 was different, and BMSC had a spontaneous osteogenesis tendency while CMSC expressed chondrogenic marker even without TGF-beta stimulation. BMSC demonstrated a paracrine effect on modulating human degenerated NP cells towards a non-degenerative phenotype in stimulating cell proliferation, slightly enhancing proteoglycan production, upregulating KRT19 while downregulating MMP12. Compared with BMSC, a higher paracrine effect of CMSC was disclosed in modulating the phenotype of NP cells in all aspects tested, and an intrinsic higher expression on CMSC of 'potential NP markers', including KRT19, KRT18 and CD55, but lower expression of osteogenic markers, including RUNX2 and ALPL, was revealed, which indicate a higher potential of CMSC for future clinical application to treat IVD degeneration diseases. KRT19 and MMP12 were also confirmed to be the highest differentially expressed candidate genes between cultured scoliosis and degenerated human NP cells, indicating a high indicator potential of NP degeneration. Furthermore, a subpopulation was detected in the degenerated NP cells that possessed macrophage-like phenotype and activities, which may play a role in the pathogenesis of
