Effects of Design Factors and Microenvironment on Mesenchymal Stem Cells and Nucleus Pulposus Cells for Intervertebral Disc Tissue Engineering

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ISBN 13 : 9780355144796
Total Pages : 157 pages
Book Rating : 4.1/5 (447 download)

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Book Synopsis Effects of Design Factors and Microenvironment on Mesenchymal Stem Cells and Nucleus Pulposus Cells for Intervertebral Disc Tissue Engineering by : Ann Ouyang

Download or read book Effects of Design Factors and Microenvironment on Mesenchymal Stem Cells and Nucleus Pulposus Cells for Intervertebral Disc Tissue Engineering written by Ann Ouyang and published by . This book was released on 2017 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt: Intervertebral disc degeneration is a common and significant health concern that often leads to low back pain and worker disability. Disc degeneration is often irreversible, and current treatments do not adequately restore cell health or biomechanical function. Tissue engineering strategies are a possible solution to regenerate disc matrix, but one challenge for regenerating tissue is the degenerative disc microenvironment, which is characterized by inflammation, hypoxia, low glucose, low pH, and high osmolality. This research focuses on the effect of design factors on tissue-engineered constructs in the context of the disc microenvironment.

Tissue Engineering For Degenerative Intervertebral Discs

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Publisher : World Scientific
ISBN 13 : 9813238585
Total Pages : 160 pages
Book Rating : 4.8/5 (132 download)

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Book Synopsis Tissue Engineering For Degenerative Intervertebral Discs by : Jun Zou

Download or read book Tissue Engineering For Degenerative Intervertebral Discs written by Jun Zou and published by World Scientific. This book was released on 2019-03-08 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Cells and Biomaterials for Intervertebral Disc Regeneration

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Publisher : Springer Nature
ISBN 13 : 3031025806
Total Pages : 96 pages
Book Rating : 4.0/5 (31 download)

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Book Synopsis Cells and Biomaterials for Intervertebral Disc Regeneration by : Sibylle Grad

Download or read book Cells and Biomaterials for Intervertebral Disc Regeneration written by Sibylle Grad and published by Springer Nature. This book was released on 2022-06-01 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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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Publisher : Morgan & Claypool Publishers
ISBN 13 : 1608454649
Total Pages : 96 pages
Book Rating : 4.6/5 (84 download)

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Book Synopsis Cells and Biomaterials for Intervertebral Disc Regeneration by : Sibylle Grad

Download or read book Cells and Biomaterials for Intervertebral Disc Regeneration written by Sibylle Grad and published by Morgan & Claypool Publishers. This book was released on 2010 with total page 96 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Engineering Nucleus Pulposus Cell-matrix Interactions with Laminin Ligands for Tissue Regeneration

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ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (138 download)

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Book Synopsis Engineering Nucleus Pulposus Cell-matrix Interactions with Laminin Ligands for Tissue Regeneration by : Julie Elizabeth Speer

Download or read book Engineering Nucleus Pulposus Cell-matrix Interactions with Laminin Ligands for Tissue Regeneration written by Julie Elizabeth Speer and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Low back pain and degenerative conditions of the intervertebral disc (IVD) represent major global socioeconomic and medical burdens. The structures that comprise the IVD including the anulus fibrosis and the nucleus pulposus (NP) work together to stabilize the axial skeleton and distribute mechanical forces. However, the degenerative cascade, which is thought to begin with changes to the NP, results in alterations to the disc that can be seen across length scales including elongated cell shapes, tissue dehydration, and loss of disc height. Patients who present clinically with these changes may also experience altered biomechanics, pain upon motion, impairments to their physical function, or associated disabilities. The NP has a limited intrinsic ability for repair, and therefore, biomaterial strategies are of interest as disease modifying, therapeutic options for repairing the tissue and delivering cell sources to defect sites. Cells, including NP cells, are able to sense and respond to cues from both native and engineered microenvironments. As a function of IVD degeneration and with the stiffening of the surrounding extracellular matrix, NP cells shift from an anabolic to a catabolic state and concomitantly become more elongated, lose their characteristic vacuoles, and demonstrate altered gene expression profiles. Previous studies have demonstrated an ability for laminin-presenting hydrogels to promote NP cells to assume behaviors characteristic of the juvenile phenotype including robust clustering of rounded cells, biosynthesis of sulfated glycosaminoglycans amongst other extracellular matrix proteins, and expression of NP cell phenotypic markers. While these effects have previously been observed, the mechanisms underlying the NP cell-laminin interactions have remained unclear. Understanding the interactions between NP cells and laminins provides insights into the mechanobiology of degenerative NP cells and can be used to inform the design of biomaterials for intervertebral disc regeneration. The studies presented in this dissertation aimed to elucidate the integrin subunits which facilitate the interactions between laminin-presenting biomaterials and degenerative human NP cells and the role of integrins in modulating NP cell behaviors. The results demonstrate that integrin [alpha]3 is a primary mediator of NP cell interactions to full-length laminin and that blocking this integrin subunit reduces intracellular signaling, biosynthesis, expression of NP cell markers, and promotes altered cytoskeletal organization. Integrin subunits were also shown to mediate cell attachment to a library of hydrogels formulated by conjugating laminin-mimetic peptides to a poly(ethylene) glycol (PEG) backbone. Data presented herein also demonstrate that stiff (10.5 kPa) peptide-functionalized hydrogels were able to promote similar cell behaviors as soft (0.3 kPa) PEG gels presenting full-length laminin. This finding indicates that biomaterials can be formulated that leverage the advantages of both short peptides (controlled sites of cellular interaction and economic value) and stiff in situ forming hydrogels (improved injection and mechanical properties, no UV crosslinking) while eliciting similar effects as soft gels made with the full-length protein. Furthermore, culture on a PEG-peptide gel induced global transcriptomic changes in degenerative NP cells including an upregulation of genes associated with notochordal morphogenesis and a concomitant downregulation of genes related to cell cycle progression and cellular contractility. Overall, this dissertation serves to identify the integrin subunits by which NP cells interact with laminin-presenting substrates and the signaling pathways that transduce cues from the extracellular microenvironment to regulate cell behaviors and drive the juvenile NP cell phenotype. Additionally, the results of both mechanistic and exploratory studies characterize clinically relevant biomaterials which could be utilized to deliver cells to the degenerative disc space and to promote tissue regeneration and reversal of pathology.

The Intervertebral Disc

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Publisher : Springer Science & Business Media
ISBN 13 : 3709115353
Total Pages : 440 pages
Book Rating : 4.7/5 (91 download)

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Book Synopsis The Intervertebral Disc by : Irving M. Shapiro

Download or read book The Intervertebral Disc written by Irving M. Shapiro and published by Springer Science & Business Media. This book was released on 2013-09-02 with total page 440 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Mesenchymal Stem Cells

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Publisher : BoD – Books on Demand
ISBN 13 : 9535136151
Total Pages : 302 pages
Book Rating : 4.5/5 (351 download)

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Book Synopsis Mesenchymal Stem Cells by : Phuc Van Pham

Download or read book Mesenchymal Stem Cells written by Phuc Van Pham and published by BoD – Books on Demand. This book was released on 2017-11-29 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Fabrication of Multi-Component Tissue for Intervertebral Disc Tissue Engineering

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Publisher :
ISBN 13 : 9781361290996
Total Pages : pages
Book Rating : 4.2/5 (99 download)

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Book Synopsis Fabrication of Multi-Component Tissue for Intervertebral Disc Tissue Engineering by : Tsz-Kit Chik

Download or read book Fabrication of Multi-Component Tissue for Intervertebral Disc Tissue Engineering written by Tsz-Kit Chik and published by . This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Fabrication of Multi-component Tissue for Intervertebral Disc Tissue Engineering" by Tsz-kit, Chik, 戚子傑, 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: Intervertebral disc tissue engineering is challenging because it involves the integration of multiple tissues with distinct structures and compositions such as lamellar annulus fibrosus, gel'like nucleus pulposus and cartilage endplate. Each of them has different compositions and different structures. It is hypothesized that integration of tissues can be enhanced with appropriate mechanical and biological stimuli. Meanwhile, effect of torsional stimulus on cell re'orientation in mesenchymal stem cell'collagen tubular constructs is investigated in this study. Furthermore, it is proposed that these findings can be used to fabricate a multicomponent unit for intervertebral disc tissue engineering. It has been demonstrated that mechanical and biological stimuli can stabilize the interface between osteogenic and chondrogenic differentiated constructs with enhanced ultimate tensile stress while the phenotype of osteogenic and chondrogenic differentiated constructs were maintained. Scanning electronic microscopic images have shown aligned collagen fibrils and presence of calcium at the interface, indicating the possibility of the formation of a calcified zone. In addition, it is proven that torsional stimulus triggered re'orientation of mesenchymal stem cells in collagen lamellae towards a preferred angle. Cell alignments were confirmed by using a MatLab'based program to analyze the actin filament and the cell alignment via Phalloidin and Hematoxylin staining, respectively. Cells and actin filaments were inclined around 30o from the vertical axis, while cells and filaments in the control group (static loading) aligned along the vertical axis. Furthermore, a double'layers bioengineered unit was fabricated, with intact osteogenic differentiated parts at both ends. Comparatively higher cell density was observed at the interface between layers, demonstrating the interactions between layers, while the phenotype of each part was maintained in 14 days culture. This study concludes that a multi'components bioengineered unit with preferred cell alignments can be fabricated. This provides new insights to future development of bioengineered spinal motion segment for treating late stage disc degeneration. DOI: 10.5353/th_b4784944 Subjects: Intervertebral disk prostheses Tissue engineering - Materials

Development and Validation of a Hydrostatic Pressure Bioreactor for Cell Culture: Applications in Intervertebral Disc and Mesenchymal Stem Cells

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Publisher :
ISBN 13 : 9780494263402
Total Pages : 120 pages
Book Rating : 4.2/5 (634 download)

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Book Synopsis Development and Validation of a Hydrostatic Pressure Bioreactor for Cell Culture: Applications in Intervertebral Disc and Mesenchymal Stem Cells by : Troy Justin Eggum

Download or read book Development and Validation of a Hydrostatic Pressure Bioreactor for Cell Culture: Applications in Intervertebral Disc and Mesenchymal Stem Cells written by Troy Justin Eggum and published by . This book was released on 2007 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt: Degeneration of the intervertebral disc (IVD) is a significant cause of pain and immobility for many people. Tissue engineering with mesenchymal stem cells (MSC) offers promise for repair or regeneration of disc tissue if they can be encouraged to differentiate to a nucleus pulposus phenotype. The cells were exposed to conditions approximating the in vivo extracellular environment of the IVD; low glucose (2.5 mg/mL), 5% hypoxia, and medium conditioned by the cells of the nucleus pulposus (notochordal and chondrocyte-like). A novel hydrostatic pressure bioreactor was designed and validated to simulate physiologic-range pressures (1MPa at 0.5 Hz and static) to in vitro cultures of MSC. These conditions were compared to the "standard" cell culture conditions of 4.5 mg/mL glucose, 20% oxygen, no hydrostatic pressure, and a "neutral" conditioned medium. The bioreactor was shown to not adversely affect cell culture and MSC were sensitive to all factors tested.

Genetic Engineering of Mesenchymal Stem Cells

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Publisher : Springer Science & Business Media
ISBN 13 : 140203959X
Total Pages : 173 pages
Book Rating : 4.4/5 (2 download)

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Book Synopsis Genetic Engineering of Mesenchymal Stem Cells by : Jan A. Nolta

Download or read book Genetic Engineering of Mesenchymal Stem Cells written by Jan A. Nolta and published by Springer Science & Business Media. This book was released on 2006-08-29 with total page 173 pages. Available in PDF, EPUB and Kindle. Book excerpt: MSC (mesenchymal stem cells) have been reported to initiate revascularization after injury, to facilitate engraftment of blood-forming stem cells, and to reduce the incidence of graft-vs. host disease through their immune-suppressive qualities. Finally, bone marrow-derived MSC have been reported to home to areas of solid tumor revascularization, and thus may be used as delivery vehicles to target ablative agents into dividing tumor cells. Recently the characteristics of human MSC from adipose (fat) tissue have also been identified. The possibility of repairing tissues, speeding stem cell engraftment, and targeting solid tumors for specific killing, using MSC easily harvested from bone marrow, or better yet, from unwanted fat tissue, holds broad appeal, and is an intriguing possibility that could have dramatic effect on health care. This book has information on how to isolate, grow, and characterize MSC from marrow and fat, and gives important insight into how these cells may be used for gene delivery and cellular therapies in the future. Updates on emerging clinical trials are given.

Microenvironment-Derived Stem Cell Plasticity

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Publisher : Frontiers Media SA
ISBN 13 : 2889453448
Total Pages : 116 pages
Book Rating : 4.8/5 (894 download)

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Book Synopsis Microenvironment-Derived Stem Cell Plasticity by : Jelena Krstic

Download or read book Microenvironment-Derived Stem Cell Plasticity written by Jelena Krstic and published by Frontiers Media SA. This book was released on 2017-12-21 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasticity is the hallmark of stem cells. At the same time, stem cells, like any other cell type, are influenced by their microenvironment and respond to it accordingly. A specific microenvironment is defined by a variety of factors, including biological and chemical factors, cell-cell interactions, but also metabolic and mechanical cues. Such dynamic and specialized microenvironment where the stem cells reside is considered a stem cell niche. Tissue injury as well as malignant tissue alterations lead to changes in the niche influencing the plasticity and biology of residing stem cells. Similarly, the niche changes upon tissue damage, which eventually induces differentiation of stem cells and ultimately regeneration of the tissue.

Mesenchymal Stem Cells and Skeletal Regeneration

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Publisher : Academic Press
ISBN 13 : 0124081312
Total Pages : 73 pages
Book Rating : 4.1/5 (24 download)

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Book Synopsis Mesenchymal Stem Cells and Skeletal Regeneration by : Peter Giannoudis

Download or read book Mesenchymal Stem Cells and Skeletal Regeneration written by Peter Giannoudis and published by Academic Press. This book was released on 2013-02-20 with total page 73 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells and Skeletal Regeneration covers our current understanding of the role of mesenchymal stem cells (MSCs) and other mesenchymal progenitors in skeletal regeneration, encompassing bone, cartilage and whole joint regeneration. The expansion reflects developments in the field to include data on the use of MSCs in drug development, growth factors, scaffolds and biomechanical manipulations for skeletal trauma and diseases, including osteoporosis and arthritis. Written for an audience of clinicians and young researchers who are exposed to MSCs in their work, this work summarizes recent findings pertaining to the definition and characterization of MSCs in skeletal tissues and discusses the mechanisms of their actions in regeneration of bone in vivo. The authors describe recent findings pertaining to the efficacy of MSC therapies in animal models and in human clinical trials and bring together literature showing that the ways MSCs are extracted, expanded and implanted can considerably affect bone formation outcomes. Finally, it presents the latest knowledge on the nature of native MSCs in skeletal tissues, which provide a platform for novel in situ tissue regeneration approaches for systemic bone disease such as osteoporosis. - Focuses specifically on the use of stem cells in skeletal tissue generation for a broad audience of stem cell, cancer, and bone biologists, orthopedists, oncologists, and regenerative medicine specialists - Provides a short historical 'detour' and foundational information on founding concepts, discoveries and personalities in MSC research - Assists a new generation of scientists and clinicians in digesting the multitude of journal articles on the topic by providing easily-absorbed and condensed foundational context

Tissue Engineering of the Intervertebral Disc Using Chemical and Mechanical Stimulation of Mesenchymal Stem Cells

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Publisher :
ISBN 13 :
Total Pages : 272 pages
Book Rating : 4.:/5 (1 download)

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Book Synopsis Tissue Engineering of the Intervertebral Disc Using Chemical and Mechanical Stimulation of Mesenchymal Stem Cells by : Katherine Deline Hudson

Download or read book Tissue Engineering of the Intervertebral Disc Using Chemical and Mechanical Stimulation of Mesenchymal Stem Cells written by Katherine Deline Hudson and published by . This book was released on 2016 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: The intervertebral disc (IVD) is a composite structure that allows bending, twisting of and load transfer through the spine. Disc damage often begins with tears in the outer annulus fibrosus (AF), allowing the inner nucleus pulposus (NP) to herniate through the weakened AF. If this condition is allowed to continue, full disc degeneration will result. Current treatment options are limited, and invasive surgical intervention can cause further degradation of the adjacent discs. This dissertation discusses how the pillars of tissue engineering are used to develop constructs for whole intervertebral disc replacement. Specifically, it describes the effects of chemical (chapters 4 and 5) and mechanical (chapter 2) stimulation, cell source (chapter 3), and scaffold materials (appendix A) on the development of tissue engineered IVDs both in vitro and in vivo.

Intervertebral Disc Regeneration Using Mesenchymal Stem Cells

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Publisher : Open Dissertation Press
ISBN 13 : 9781374665255
Total Pages : pages
Book Rating : 4.6/5 (652 download)

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Book Synopsis Intervertebral Disc Regeneration Using Mesenchymal Stem Cells by : Fan Yang

Download or read book Intervertebral Disc Regeneration Using Mesenchymal Stem Cells written by Fan Yang and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Potential of Bone Marrow and Umbilical Cord Derived Mesenchymal Stem Cells in Intervertebral Disc Repair

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Publisher : Open Dissertation Press
ISBN 13 : 9781361276341
Total Pages : pages
Book Rating : 4.2/5 (763 download)

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Book Synopsis Potential of Bone Marrow and Umbilical Cord Derived Mesenchymal Stem Cells in Intervertebral Disc Repair by : Fengjuan Lu

Download or read book Potential of Bone Marrow and Umbilical Cord Derived Mesenchymal Stem Cells in Intervertebral Disc Repair written by Fengjuan Lu and published by Open Dissertation Press. This book was released on 2017-01-26 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

In Vitro Culture System to Study Human Mesenchymal Stem Cell/nucleus Pulposus Cell Interactions

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ISBN 13 :
Total Pages : 193 pages
Book Rating : 4.:/5 (711 download)

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Book Synopsis In Vitro Culture System to Study Human Mesenchymal Stem Cell/nucleus Pulposus Cell Interactions by : Sandra Strassburg

Download or read book In Vitro Culture System to Study Human Mesenchymal Stem Cell/nucleus Pulposus Cell Interactions written by Sandra Strassburg and published by . This book was released on 2010 with total page 193 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Intervertebral Disc Regeneration

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Publisher : Mdpi AG
ISBN 13 : 9783036527543
Total Pages : 138 pages
Book Rating : 4.5/5 (275 download)

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Book Synopsis Intervertebral Disc Regeneration by : Benjamin Gantenbein

Download or read book Intervertebral Disc Regeneration written by Benjamin Gantenbein and published by Mdpi AG. This book was released on 2022-01-11 with total page 138 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.