June 15, 2021

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Resident Stem Cells and Regenerative Therapy

Resident Stem Cells and Regenerative Therapy
Author : Regina Coeli dos Santos Goldenberg,Antonio Carlos Campos de Carvalho
Publisher : Academic Press
Release Date : 2012
Category : Science
Total pages :270
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In the last 3 decades, stem cells have greatly impacted the scientific and lay communities, providing huge advances in the treatment of devastating human diseases, including myocardial infarction, diabetes, muscular dystrophy, cystic fibrosis, cirrhosis, and osteoporosis. Alongside debates of induced pluripotent stem cells and embryonic stem cells has been the discovery of adult stem cells in many different tissues. While these organ resident or progenitor stem cells offer prospects to contribute to tissue regeneration, they also present challenges because of the complexity of organ structures. This book will present the main findings to date and the important factors to be considered when considering resident stem cells in regenerative therapies. Chapters on cardiac, brain, neural, liver, kidney, skeletal muscle, bone, pancreatic, skin, and lung resident stem cells will assist in defining the level of success that has been achieved and the direction for the road ahead. With contributions from leading laboratories, open questions related to resident stem cells and regenerative therapies will also be presented for debate. Highlights basic research in tissue specific stem cells, experiments with animal models and clinical trials that are transforming the field of regeneration Provides a clear understanding of endogenous stem cells, their role in current regenerative therapies, and prospects for future research Reports on the main-stream clinical approaches and in vivo experiments published in primary literature to help categorizes the advances in various aspects of regenerative therapy and illustrate opportunities for clinical applications

Extracellular Matrix Enhances Therapeutic Effects of Stem Cells in Regenerative Medicine

Extracellular Matrix Enhances Therapeutic Effects of Stem Cells in Regenerative Medicine
Author : Yan Nie
Publisher : Unknown
Release Date : 2016
Category : Science
Total pages :129
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Stem cell therapy is a promising option for regenerative of injured or diseased tissues. However, the extremely low survival and engraftment of transplanted cells and the obviously inadequate recruitment and activation of the endogenous resident stem cells are the major challenges for stem cell therapy. Fortunately, recent progresses show that extracellular matrix (ECM) could not only act as a spatial and mechanical scaffold to enhance cell viability but also provide a supportive niche for engraftment or accelerating stem cell differentiation. These findings provide a new approach for increasing the efficiency of stem cell therapy and may lead to substantial changes in cell administration. In order to take a giant stride forward in stem cell therapy, we need to know much more about how the ECM affects cell behaviours. In this chapter, we provide an overview of the influence of ECM on regulating stem cell maintenance and differentiation. Moreover, the enhancement of supportive microenvironment function of natural or synthetic ECMs in stem cell therapy is discussed.

Resident Stem Cells and Regenerative Therapy

Resident Stem Cells and Regenerative Therapy
Author : Regina Coeli dos Santos Goldenberg,Antonio Carlos Campos de Carvalho
Publisher : Academic Press
Release Date : 2012-12-31
Category : Technology & Engineering
Total pages :304
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In the last 3 decades, stem cells have greatly impacted the scientific and lay communities, providing huge advances in the treatment of devastating human diseases, including myocardial infarction, diabetes, muscular dystrophy, cystic fibrosis, cirrhosis, and osteoporosis. Alongside debates of induced pluripotent stem cells and embryonic stem cells has been the discovery of adult stem cells in many different tissues. While these organ resident or progenitor stem cells offer prospects to contribute to tissue regeneration, they also present challenges because of the complexity of organ structures. This book will present the main findings to date and the important factors to be considered when considering resident stem cells in regenerative therapies. Chapters on cardiac, brain, neural, liver, kidney, skeletal muscle, bone, pancreatic, skin, and lung resident stem cells will assist in defining the level of success that has been achieved and the direction for the road ahead. With contributions from leading laboratories, open questions related to resident stem cells and regenerative therapies will also be presented for debate. Highlights basic research in tissue specific stem cells, experiments with animal models and clinical trials that are transforming the field of regeneration Provides a clear understanding of endogenous stem cells, their role in current regenerative therapies, and prospects for future research Reports on the main-stream clinical approaches and in vivo experiments published in primary literature to help categorizes the advances in various aspects of regenerative therapy and illustrate opportunities for clinical applications

Stem Cell Biology and Regenerative Medicine in Ophthalmology

Stem Cell Biology and Regenerative Medicine in Ophthalmology
Author : Stephen Tsang
Publisher : Springer Science & Business Media
Release Date : 2012-12-09
Category : Science
Total pages :188
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Patient specific and disease specific stem cell lines have already introduced groundbreaking advances into the research and practice of ophthalmology. This volume provides a comprehensive and engaging overview of the latest innovations in the field. Twelve chapters discuss the fastest growing areas in ophthalmological stem cell research, from disease modelling, drug screening and gene targeting to clinical genetics and regenerative treatments. Innovative results from stem cell research of the past decade are pointing the way toward practicable treatments for retinitis pigmentosa, age related macular degeneration, and Stargardt disease. What future directions will stem cell research take? Researchers, graduate students, and fellows alike will find food for thought in this insightful guide tapping into the collective knowledge of leaders in the field. Stem Cells in Ophthalmology is part of the Stem Cells in Regenerative Medicine series dedicated to discussing current challenges and future directions in stem cell research.

The Promises and Challenges of Regenerative Medicine

The Promises and Challenges of Regenerative Medicine
Author : John Morser,S. -I. Nishikawa
Publisher : Springer
Release Date : 2014-11-28
Category : Science
Total pages :136
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Adult Stem Cells

Adult Stem Cells
Author : Donald G. Phinney
Publisher : Springer Science & Business Media
Release Date : 2011-02-11
Category : Science
Total pages :279
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This is comprehensive overview of a vital area of scientific enquiry, which covers a broad spectrum of issues. With contributions from some of the key researchers in the field, Adult Stem Cells: Biology and Methods of Analysis offers readers a historical perspective as well as unique insights into cutting-edge thoughts. The volume contextualizes the recent discovery of stem/progenitor cell populations resident in many adult tissues and organs. It confronts the complexities scientists face in trying to validate these cells, while it also describes and critically evaluates the methods currently used to assess stem cell self-renewal. The chapters also seek to distinguish this process from other aspects of cell survival, such as the regulation of life span, senescence, and immortalization at a molecular level. The monograph begins with a section that examine the basic biology of adult stem cells, including chapters on the emerging role of microRNAs in regulating their fate and the molecular mechanisms that govern their self-renewal, the book moves on to analyze the varying methodologies employed in characterizing these elusive elements of our genetic make-up. The second section details in-vivo lineage tracing of tissue-specific stem cells, explores the neural stem cell paradigm, and considers the function of ABC transporters and aldehyde dehydrogenase in adult stem-cell biology. The final section shifts the focus to the life-span regulation and immortalization and features a chapter on the cancer stem cell paradigm. This is an authoritative volume on one of the frontiers of genetic research, and will serve as a valuable resource, not just for established scientists but also for those now entering the field of stem cell biology.

Gene Therapy and Cell Fusion Enhances Stem Cell Mediated Cardiac Repair

Gene Therapy and Cell Fusion Enhances Stem Cell Mediated Cardiac Repair
Author : Pearl Jennine Quijada
Publisher : Unknown
Release Date : 2015
Category :
Total pages :130
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Cardiovascular disease is the leading cause of mortality in the United States. Myocardial infarction (MI) induces massive cellular death and leads to a decline in cardiac function. Cardiomyocytes have limited proliferative capacity sparking interests in molecular and cellular strategies to promote stem cell conversion into new cardiomyocytes. Cardiac progenitor cells (CPCs) are tissue resident stem cells that give rise to cardiomyogenic structures. Although, CPCs introduced into the heart confer improvements in cardiac function after MI, these effects are not sufficient to support complete heart regeneration and prevent heart failure. Studying molecular pathways that contribute to CPC survival and commitment is essential in advancing CPC based therapeutic approaches. Ca2+/Calmodulin-dependent protein kinase II[Delta]B (CaMKII[Delta]B) regulates survival and growth in cardiomyocytes. However, the role of CaMKII[Delta] in CPCs has not been previously explored. CPCs increase nuclear CaMKII after MI and in vitro differentiation suggesting that CaMKII[Delta]B contributes to the regulation of CPC commitment. Overexpression of CaMKII[Delta]B in CPCs reduces proliferation, enhances resistance to death and increases cardiac specific differentiation. CaMKII[Delta]B may serve as a novel modulatory kinase to promote CPC survival and commitment. Despite increasing use of stem cells for regenerative-based cardiac therapy, the optimal stem cell population(s) remains uncertain. In the past decade there has been increasing interest and characterization of stem cell populations reported to directly and/or indirectly contributes to cardiac regeneration through processes of cardiomyogenic commitment and / or release of cardioprotective paracrine factors. Future therapies require development of unprecedented concepts to enhance myocardial healing. Combinatorial cell therapy utilizing CPCs and bone marrow derived mesenchymal stem cells (MSCs) promote enhanced reparative functions in vivo. However, identifying cell specific mechanisms of cardiac repair are difficult using dual cell systems. Here, we performed cell fusion between CPCs and MSCs to obtain hybrids with combined cell characteristics called CardioChimeras. Our ideal cell therapy is to combine the beneficial properties of CPCs to undergo cardiac specific commitment as well as MSCs that foster an improved microenvironment with protective paracrine secretion.

Muse Cells

Muse Cells
Author : Mari Dezawa
Publisher : Springer
Release Date : 2019-01-05
Category : Medical
Total pages :315
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This book provides the first comprehensive account of multilineage-differentiating stress-enduring (Muse) cells, a pluripotent and non-tumorigenic subpopulation of mesenchymal stem cells (MSCs) that have the ability to detect damage signals, migrate to damaged sites, and spontaneously differentiate into cells compatible with the affected tissue, thereby enabling repair of all tissue types. The coverage encompasses everything from the basic properties of Muse cells to their tissue repair effects and potential clinical applications—for example, in acute myocardial infarction, stroke, skin injuries and ulcers, renal failure, and liver disease. An important technical chapter provides a practical and precise protocol for the isolation of Muse cells, which will enable readers to use Muse cells in their own research. In offering fascinating insights into the strategic organization of the body’s reparative function and explaining how full utilization of Muse cells may significantly enhance the effectiveness of MSC treatment, the book will be of high value for Ph.D. students, postdocs, basic researchers, clinical doctors, and industrial developers.

Multimodal Nanoparticles for Image-guided Delivery of Mesenchymal Stem Cells in the Treatment of Myocardial Infarction

Multimodal Nanoparticles for Image-guided Delivery of Mesenchymal Stem Cells in the Treatment of Myocardial Infarction
Author : Sean Sweeney
Publisher : Unknown
Release Date : 2015
Category : Coronary heart disease
Total pages :135
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One of the leading causes of death and hospital stays in the United States, myocardial infarction (MI) occurs when coronary blockages lead to downstream ischemia in the myocardium. Following the MI, the heart activates a number of pathways to repair or remodel the infarcted zone. Endothelial cells respond to ischemia by de-differentiating to form neovasculature and myofibroblasts. The resident cardiac differentiable stem cells (CDCs) are recruited via local cytokines and chemokines to the infarct zone where they too differentiate into myofibroblasts. Mesenchymal stem cells (MSCs) of the bone marrow respond to circulating factors by immobilizing to the heart and differentiating down cardiac lineages. In regenerative medicine approaches, these processes are exploited to augment the resident supply of reparative cells. Clinical trials to transplant cardiac stem cells into MI zones have been met with mixed results. When CDCs are harvested from autologous or type-matched donors, the cells are prepared with a minimum of manipulations, but the yield is quite small. Conversely, MSCs from bone marrow are highly proliferative, but the manipulations in culture required to trigger cardiac differentiation have been found to transform the cell into a more immunogenic phenotype. In addition, there is a dearth of in vivo evidence for the fate of transplanted cells. Currently, intracardiac echocardiographs are used to assess the infarcted area and to guide delivery of stem cell transplants. However, this modality is invasive, short-term, and does not image the transplanted cells directly. In this project, I addressed these shortcomings with a regenerative medicine and bioimaging approach.

Role of Stem Cells and Extracellular Matrix in the Regeneration of Skeletal Muscle

Role of Stem Cells and Extracellular Matrix in the Regeneration of Skeletal Muscle
Author : Andrew Dunn
Publisher : Unknown
Release Date : 2018
Category : Technology
Total pages :129
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Adult skeletal muscle has a remarkable capacity to initiate a rapid and extensive repair process after damage due to injury or degenerative disease. Although satellite cells are the primary skeletal muscle stem cells, there are many reports of non-satellite cell populations with myogenic capacity resident within skeletal muscle. The activity of muscle-resident stem cells during the regeneration process is tightly controlled through the dynamic interactions between intrinsic factors within the cells and extrinsic factors constituting the muscle stem cell niche. The extracellular matrix (ECM) in skeletal muscle plays an integral role in force transmission, structural maintenance, and regulation of stem cell niche. ECM interacts with stem cells either directly by binding cell surface receptors or indirectly through growth factor presentation, and maintains a balance between their quiescence, self-renewal, and differentiation. These interactions are reciprocal since the stem cells can remodel the niche and secrete or degrade ECM components. Natural ECM scaffolds, derived from decellularized tissues can influence stem cell activity both in vitro and in vivo and are widely being investigated for skeletal muscle repair. In this chapter, we discuss the regenerative potential of stem cell populations and ECM bioscaffolds in the treatment of skeletal muscle injury and disease.

Stem Cell and Biologic Scaffold Engineering

Stem Cell and Biologic Scaffold Engineering
Author : Panagiotis Mallis
Publisher : MDPI
Release Date : 2019-10-04
Category : Science
Total pages :110
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Tissue engineering and regenerative medicine is a rapidly evolving research field which effectively combines stem cells and biologic scaffolds in order to replace damaged tissues. Biologic scaffolds can be produced through the removal of resident cellular populations using several tissue engineering approaches, such as the decellularization method. Indeed, the decellularization method aims to develop a cell-free biologic scaffold while keeping the extracellular matrix (ECM) intact. Furthermore, biologic scaffolds have been investigated for their in vitro potential for whole organ development. Currently, clinical products composed of decellularized matrices, such as pericardium, urinary bladder, small intestine, heart valves, nerve conduits, trachea, and vessels, are being evaluated for use in human clinical trials. Tissue engineering strategies require the interaction of biologic scaffolds with cellular populations. Among them, stem cells are characterized by unlimited cell division, self-renewal, and differentiation potential, distinguishing themselves as a frontline source for the repopulation of decellularized matrices and scaffolds. Under this scheme, stem cells can be isolated from patients, expanded under good manufacturing practices (GMPs), used for the repopulation of biologic scaffolds and, finally, returned to the patient. The interaction between scaffolds and stem cells is thought to be crucial for their infiltration, adhesion, and differentiation into specific cell types. In addition, biomedical devices such as bioreactors contribute to the uniform repopulation of scaffolds. Until now, remarkable efforts have been made by the scientific society in order to establish the proper repopulation conditions of decellularized matrices and scaffolds. However, parameters such as stem cell number, in vitro cultivation conditions, and specific growth media composition need further evaluation. The ultimate goal is the development of “artificial” tissues similar to native ones, which is achieved by properly combining stem cells and biologic scaffolds and thus bringing them one step closer to personalized medicine. The original research articles and comprehensive reviews in this Special Issue deal with the use of stem cells and biologic scaffolds that utilize state-of-the-art tissue engineering and regenerative medicine approaches.

Human Pluripotent Stem Cell-derived Mesothelium Functions in Regenerative Medicine as a Multipotent Vascular Progenitor

Human Pluripotent Stem Cell-derived Mesothelium Functions in Regenerative Medicine as a Multipotent Vascular Progenitor
Author : Thomas Anthony Colunga
Publisher : Unknown
Release Date : 2018
Category :
Total pages :129
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The human body contains two major coelomic cavities, thoracic and abdominal, that are lined with an epithelial cell called mesothelium. Mesothelium also forms the outer layer of internal organs within these cavities and an additional protective pouch surrounding the heart called the pericardium. Mesothelium contributes to the development of the coelomic organs including the vasculature by acting as a multipotent vascular progenitor. During development and upon reactivation after injury, the mesothelium of the outer layer of organs loses its polarity and migrates to the underlying tissue in a process called epithelial-to-mesenchymal transition (EMT). After undergoing EMT, mesothelium can differentiate to vascular lineages required for the growth of new blood vessels that play an important role in organ repair and regeneration processes. For these reasons, mesothelium constitutes a resident vascular progenitor cell type found in all coelomic organs including the heart, lung, liver and gut and may have utility in regenerative medicine. Utilizing human pluripotent stem cells (hPSCs), we have developed an in vitro-derived mesothelial cell (MesoT) that can give rise to all the required vascular lineages. When using MesoT as a cellular therapeutic for a mechanically injured neonatal mouse model we uncovered its ability to incorporate into newly formed blood vessels. MesoT cells were also used to reseed the vascular network of a decellularized biological scaffold. Subsequent in vivo implantation of the newly vascularized graft displayed patency, did not thrombose and was able to perfuse blood down to the capillary bed which confirmed its utility in tissue engineering and possible corrective surgery. This work constitutes one of the first reports of a true vascular progenitor that can give rise to all required cell types of the vasculature and highlights the utility of MesoT cells in regenerative medicine.

Stem Cell Research on Cardiology

Stem Cell Research on Cardiology
Author : Robert David
Publisher : Unknown
Release Date : 2020-10
Category :
Total pages :356
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Even today, cardiovascular diseases are the main cause of death worldwide, and therapeutic approaches are very restricted. Due to the limited regenerative capabilities of terminally differentiated cardiomyocytes post injury, new strategies to treat cardiac patients are urgently needed. Post myocardial injury, resident fibroblasts begin to generate the extracellular matrix, resulting in fibrosis, and finally, cardiac failure. Recently, preclinical investigations and clinical trials raised hope in stem cell-based approaches, to be an effective therapy option for these diseases. So far, several types of stem cells have been identified to be promising candidates to be applied for treatment: cardiac progenitor cells, bone marrow derived stem cells, embryonic and induced pluripotent stem cells, as well as their descendants. Furthermore, the innovative techniques of direct cardiac reprogramming of cells offered promising options for cardiovascular research, in vitro and in vivo. Hereby, the investigation of underlying and associated mechanisms triggering the therapeutic effects of stem cell application is of particular importance to improve approaches for heart patients. This Special Issue of Cells provides the latest update in the rapidly developing field of regenerative medicine in cardiology.

Evaluation of the Potential for Repair of Degenerate Hyaline Cartilage in the Osteoarthritic Knee by Cartilage Stem Cells

Evaluation of the Potential for Repair of Degenerate Hyaline Cartilage in the Osteoarthritic Knee by Cartilage Stem Cells
Author : Larissa Nelson
Publisher : Unknown
Release Date : 2012
Category :
Total pages :129
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Osteoarthritis (OA) is a highly prevalent, debilitating disease affecting many joints including the knee. Despite the involvement of several tissues, it is believed that the articular cartilage is the primary site of pathogenesis in humans. Within this study, a new scoring system of OA was devised, incorporating the articular cartilage and underlying bone, aimed at providing a more comprehensive means of grading the severity of tissue damage. We examined changes progressively from mild to severe and were able to deduce from the scoring system that bone changes may precede those of the overlying cartilage. Immunohistochemistry was used to assess stem cell marker expression, proliferation and progressive changes within the extracellular matrix of sectioned osteochondral plugs, however no distinct pattern of change could be extrapolated, highlighting the variable nature of this taxing disease. Previous studies have demonstrated the presence of a sub-population of chondroprogenitor cells present in normal hyaline cartilage. We demonstrated in this study that a similar group of cells reside in osteoarthritic articular cartilage. We were able to isolate and expand clonally derived primary cell lines to beyond 50 population doublings whilst maintaining a chondrogenic phenotype, and demonstrated the tri-lineage potential of these cells. That said, a significant amount of variation was observed and it was, therefore, postulated that there may be a smaller cohort of viable cells within this sub-population isolated from osteoarthritic cartilage. A preliminary study was also carried out comparing chondroprogenitors from normal articular cartilage to those isolated from OA tissue. Heterogeneity was again encountered, suggesting that there was a group of OA chondroprogenitors with similar characteristics to the normal cells, which differed from the other less metabolically active cells. This finding was agreeable with the aforementioned postulation. Data from our preliminary integration study was promising as we demonstrated the potential for using these chondroprogenitor cells in combination with other cells whilst achieving successful integration. However, further work is necessary to distinguish between the cell lines with the potential for integration from those that lacked this ability, thereby eliminating the heterogeneity. The presence of viable chondroprogenitor cells in OA tissue challenges the dogma that the tissue is irrecoverable, and opens the scope for regenerative medicine using resident progenitor cells. This is an exciting prospect that could significantly contribute to articular cartilage repair.

The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration

The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration
Author : Francisco J. Rivera,Ludwig Aigner
Publisher : Frontiers Media SA
Release Date : 2018-03-13
Category :
Total pages :129
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Tissues and organs have, although sometimes limited, the capacity for endogenous repair, which is aimed to re-establish integrity and homeostasis. Tissue repair involves pro- and anti-inflammatory processes, new tissue formation and remodelling. Depending on the local microenvironment, tissue repair results either in scar tissue formation or in regeneration. The latter aims to recapitulate the original tissue structure and architecture with the proper functionality. Although some organisms (such as planarians) have a high regenerative capacity throughout the body, in humans this property is more restricted to a few organs and tissues. Regeneration in the adult is possible in particular through the existence of tissue-resident pools of stem/progenitor cells. In response to tissue damage, these cells are activated, they proliferate and migrate, and differentiate into mature cells. Angiogenesis and neovascularization play a crucial role in tissue repair. Besides providing with oxygen and nutrients, angiogenesis generates a vascular niche (VN) consisting of different blood-derived elements and endothelial cells surrounded by basement membrane as well as perivascular cells. The newly generated VN communicates with the local stem/progenitor cells and contributes to tissue repair. For example, platelets, macrophages, neutrophils, perivascular cells and other VN components actively participate in the repair of skin, bone, muscle, tendon, brain, spinal cord, etc. Despite these observations, the exact role of the VN in tissue repair and the underlying mechanisms are still unclear and are awaiting further evidence that, indeed, will be required for the development of regenerative therapies for the treatment of traumatic injuries as well as degenerative diseases.