Effect Of Chondrocyte Stem Cell Interactions On Chondrogenesis Of Mesenchymal Stem Cells
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| Author | : Gunjan Gupta |
| Publisher | : |
| Total Pages | : 137 |
| Release | : 2009 |
| Genre | : |
| ISBN | : |
Mesenchymal stem cells (MSCs) have been considered as a promising cell source for cartilage tissue regeneration owing to their intrinsic musculoskeletal differentiation potential. A successful MSC-derived hyaline cartilage tissue should be structurally and functionally similar to native cartilage. During embryonic development morphogens have been shown to play a critical role in cartilage tissue formation. In this study we thus investigated the effect of chondrocyte-MSC interactions in the form of soluble morphogens on chondrogenic differentiation of MSCs using a co-culture system, wherein the hMSCs-laden hydrogels and chondrocytes were not in physical contact but can still exchange cell secreted factors. Healthy chondrocytes and osteoarthritic (OA) chondrocytes were able to induce chondrogenesis of hMSCs as analyzed by biochemical assays, gene analysis, and histology. We further explored the role of PTHrP and TGF-[beta]1 on chondrogenesis of hMSCs and found that in their combined presence, hMSCs had an upregulated expression of cartilage specific markers such as collagen type II and aggrecan and enhanced extracellular matrix production. Even in the absence of TGF-[beta]1 co-culture could induce chondrogenesis. A detailed analysis indicated that TGF-[beta]1 promotes proliferation and chondrogenic differentiation of MSCs, while PTHrP regulates hypertrophy. Mass spectrometry analysis underlined the crucial role of cross-talk on cell secreted morphogens. Extracellular histones inducing growth hormone production formed a major part of the morphogens unique to a co-culture system which is known to promote chondrogenesis. Our experimental observations along with numerical analysis indicated the crucial role of diffusion-mediated morphogenic concentration on chondrogenesis of MSCs.
| Author | : Jeremy James Lim |
| Publisher | : |
| Total Pages | : |
| Release | : 2012 |
| Genre | : Cell differentiation |
| ISBN | : |
Tissue engineering strategies represent exciting potential therapies to repair cartilage injuries; however, difficulty regenerating the complex extracellular matrix (ECM) organization of native cartilage remains a significant challenge. Cartilaginous ECM molecules, specifically chondroitin sulfate (CS) glycosaminoglycan, may possess the ability to promote and direct MSC differentiation down a chondrogenic lineage. CS may interact with the stem cell microenvironment through its highly negative charge, generation of osmotic pressure, and sequestration of growth factors; however, the role of CS in directing differentiation down a chondrogenic lineage remains unclear. The overall goal of this dissertation was to develop versatile biomaterial platforms to control CS presentation to mesenchymal stem cells (MSCs) in order to improve understanding of the interactions with CS that promote chondrogenic differentiation. To investigate chondrogenic response to a diverse set of CS materials, progenitor cells were cultured in the presence of CS proteoglycans and CS chains in a variety of 2D and 3D material systems. Surfaces were coated with aggrecan proteoglycan to alter cell morphology, CS-based nano- and microspheres were developed as small particle carriers for growth factor delivery, and desulfated chondroitin hydrogels were synthesized to examine electrostatic interactions with growth factors and the role of sulfation in the chondrogenic differentiation of MSCs. Together these studies provided valuable insight into the unique ability of CS-based materials to control cellular microenvironments via morphological and material cues to promote chondrogenic differentiation in the development of tissue engineering strategies for cartilage regeneration and repair.
| Author | : Phuc Van Pham |
| Publisher | : Springer |
| Total Pages | : 316 |
| Release | : 2017-01-24 |
| Genre | : Science |
| ISBN | : 3319401440 |
This invaluable resource discusses clinical applications with effects and side-effects of applications of stem cells in bone and cartilage regeneration. Each chapter is contributed by a pre-eminent scientist in the field and covers such topics as skeletal regeneration by mesenchymal stem cells, clinical improvement of mesenchymal stem cell injection in injured cartilage and osteoarthritis, Good manufacturing practice (GMP), minimal critera of stem cells for clinical applications, future directions of the discussed therapies and much more. Bone & Cartilage Regeneration and the other books in the Stem Cells in Clinical Applications series will be invaluable to scientists, researchers, advanced students and clinicians working in stem cells, regenerative medicine or tissue engineering.
| Author | : Kyriacos A. Athanasiou |
| Publisher | : Morgan & Claypool Publishers |
| Total Pages | : 183 |
| Release | : 2010 |
| Genre | : Medical |
| ISBN | : 1598298755 |
Cartilage injuries in children and adolescents are increasingly observed, with roughly 20% of knee injuries in adolescents requiring surgery. In the US alone, costs of osteoarthritis (OA) are in excess of $65 billion per year (both medical costs and lost wages). Comorbidities are common with OA and are also costly to manage. Articular cartilage's low friction and high capacity to bear load makes it critical in the movement of one bone against another, and its lack of a sustained natural healing response has necessitated a plethora of therapies. Tissue engineering is an emerging technology at the threshold of translation to clinical use. Replacement cartilage can be constructed in the laboratory to recapitulate the functional requirements of native tissues. This book outlines the biomechanical and biochemical characteristics of articular cartilage in both normal and pathological states, through development and aging. It also provides a historical perspective of past and current cartilage treatments and previous tissue engineering efforts. Methods and standards for evaluating the function of engineered tissues are discussed, and current cartilage products are presented with an analysis on the United States Food and Drug Administration regulatory pathways that products must follow to market. This book was written to serve as a reference for researchers seeking to learn about articular cartilage, for undergraduate and graduate level courses, and as a compendium of articular cartilage tissue engineering design criteria. Table of Contents: Hyaline Articular Cartilage / Cartilage Aging and Pathology / In Vitro / Bioreactors / Future Directions
| Author | : Rik Derynck |
| Publisher | : CSHL Press |
| Total Pages | : 1108 |
| Release | : 2008 |
| Genre | : Transforming growth factors-beta |
| ISBN | : 0879697520 |
Transforming growth factor-[beta] (TGF-[beta]), identified nearly three decades ago, is a secreted polypeptide that functions in critical cell cycle processes, including cellular proliferation, differentiation, and development: It belongs to a large protein family that, in humans, contains 33 members, including activins, inhibins, bone morphogenetic proteins, growth and differentiation factors, and Mullerian inhibiting substance. This volume draws on the world's leading laboratories to comprehensively cover all aspects of the biology of TGF-[beta] and related factors. In addition to providing historical and background information, it describes the cell biology and signaling pathways of TGF-[beta] members in detail, including the roles of TGF-[beta] factors in the development and physiology of humans and model organisms. The last few chapters are devoted to the role of TGF-[beta] members in cancer and other diseases, as well as the possibilities for therapeutics based on knowledge of signaling pathways and macromolecular structures. It serves as a comprehensive reference work for both specialists and researchers less familiar with the field.
| Author | : Yaoliang Tang |
| Publisher | : Academic Press |
| Total Pages | : 287 |
| Release | : 2015-09-02 |
| Genre | : Science |
| ISBN | : 0128004975 |
Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. - Introduces the MSC-exosome mediated cell-cell communication - Covers the major functional benefits in current MSC-derived exosome studies - Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies
| Author | : Alexander J. Neumann |
| Publisher | : |
| Total Pages | : |
| Release | : 2013 |
| Genre | : |
| ISBN | : |
Adult articular cartilage has a limited repair capacity. This leads to an increasing demand for optimised repair techniques. Furthermore, current procedures to regenerate articular cartilage fail to achieve sufficient results. Previous work within our group suggested that combination of functional tissue engineering and gene transfer represents a promising alternative approach. In this thesis, different viral gene transfer methods were investigated and optimised. A clinically relevant three dimensional transduction model was developed. These results were directly implemented in further work aiming to investigate the combined effect of multiaxial mechanical stimulation and adenoviral-mediated over-expression of bone morphogenetic protein 2 on human chondroprogenitor cell chondrogenesis and progression towards hypertrophy. Two cell sources were investigated, namely human mesenchymal stem cells and human articular cartilage progenitor cells. The combined approached enhanced human mesenchymal stem cell chondrogenesis. Yet, it was not possible to completely prevent progression towards hypertrophy. For human articular cartilage progenitor cells, over-expression of bone morphogenetic protein 2 did enhance their chondrogenic differentiation potential. However, mechanical stimulation alone, in the absence of exogenous growth factors, led to stable chondrogenic induction without signs of hypertrophic differentiation. This suggests these cells should be further investigated. Additionally, the potential of Dorsomorphin, as possible agent to block hypertrophic differentiation by inhibition of bone morphogenetic protein signalling, was investigated in a fibrin polyurethane composite system, using human mesenchymal stem cells. As opposed to the pellet culture model, application of Dorsomorphin led to a cytotoxic effect which decreased the general differentiation potential. Finally, the chondrogenic potential of the two cell types was directly compared, using the pellet culture model. Under serum-free conditions, human articular cartilage progenitor cells were not able to undergo chondrogenesis. The reasons for this remain to be elucidated. The combined results of the thesis can help to develop a novel one-step procedure to treat articular cartilage defects.
| Author | : Mohan C Vemuri |
| Publisher | : Humana Press |
| Total Pages | : 534 |
| Release | : 2017-05-04 |
| Genre | : Science |
| ISBN | : 9781493957798 |
Mesenchymal Stem Cells have seen an unprecedented level of interest in the last decade, primarily due to their relative ease of isolation, the large numbers of cells present in the adult, and the ability to propagate these cells in culture. In Mesenchymal Stem Cell Assays and Applications, expert researchers from across the globe explore the latest techniques to propagate, characterize, and engineer this special cell type. Chapters outline a set of protocols and assays used by leading investigators in the field, providing standards that can be applied by all researchers to the population of cells used in their experiments. Composed in the highly successful Methods in Molecular BiologyTM series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Ground-breaking and current, Mesenchymal Stem Cell Assays and Applications is a necessary handbook for all researchers working with this ambiguous population of cells.
| Author | : Massimo Sabatini |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 362 |
| Release | : 2008-02-01 |
| Genre | : Medical |
| ISBN | : 1592598102 |
Osteoarthritis (OA), the most common form of arthritis, is generally characterized by a slowly progressive degeneration of articular cartilage, particularly in the weight-bearing joints. It has a stronger prevalence in women, and its incidence increases with age. OA is a major and growing health concern in developed countries, owing to steadily increasing life expectancy and the demand for better quality of life. Because of its chronic nature and nonfatal outcome, OA affects the growing population of the elderly over an increasing time span. Moreover, despite its relatively benign character, OA is one of the most disabling diseases; it is responsible for increasing financial and social burdens in terms of medical treatments, forced inactivity, loss of mobility, and dependence. Despite a growing awareness of OA as a medical problem that has yet to reach its maximum impact on society, there is a surprising absence of effective medical treatments beyond pain control and surgery. So far, only symptom-modifying drugs are available, while there remains a major demand for disease-modifying treatments of proven clinical efficacy. This demand will hopefully be met in the future by some of the drugs that have been pressed into development and are now at different stages of clinical investigation. Nevertheless, the current lack of effective treatments reflects a still insufficient knowledge of cartilage with respect to its metabolism, interactions with other joint tissues, and causes and mechanisms (possibly of very different nature) leading to failure of its turnover.
| Author | : Francoise Firmin |
| Publisher | : Thieme |
| Total Pages | : 601 |
| Release | : 2016-12-01 |
| Genre | : Medical |
| ISBN | : 1638534853 |
FIVE STARS from Doody's Star Ratings™ This book details the surgical techniques of Dr. Francoise Firmin, a recognized thought leader in auricular surgery. It contains her "trade secrets" that have been distilled over many years of practice and is abundantly illustrated with over 1000 colour photographs and drawings. The book includes operative and lecture video plus an eBook. This practical, authoritative book will be an essential purchase to all surgeons who operate on the ear.
