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In the Arabidopsis root, growth is sustained by the meristem. Signalling from organiser cells, also termed the quiescent centre (QC), is essential for the maintenance and replenishment of the stem cells. Here, we highlight three publications from the founder of the concept of the stem cell niche in Arabidopsis and a pioneer in unravelling regulatory modules governing stem cell specification and maintenance, as well as tissue patterning in the root meristem: Ben Scheres. His research has tremendously impacted the plant field. We have selected three publications from the Scheres legacy, which can be considered a breakthrough in the field of plant developmental biology. van den Berg et al. (1995) and van den Berg et al. (1997) uncovered that positional information-directed patterning. Sabatini et al. (1999), discovered that auxin maxima determine tissue patterning and polarity. We describe how simple but elegant experimental designs have provided the foundation of our current understanding of the functioning of the root meristem.
The complexity of the human brain creates a spectrum of sophisticated behavioral repertoires, such as language, tool use, self-awareness, symbolic thought, cultural learning, and consciousness. Understanding how the human brain achieves that has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition and disease states. Human pluripotent stem cells could differentiate into specialized cell types and tissues in vitro. From this pluripotent state, it is possible to generate models of the human brain, such as brain organoids. The recent observation that brain organoids can spontaneously develop complex neural network activity in a dish can help one understand how neural network oscillations evolve and vary between normal and disease states. Moreover, this finding can be leveraged to other applications outside medicine, including engineering and artificial intelligence. However, as the brain model technology becomes more complex, it raises a series of ethical and moral dilemmas. This article discusses the status of this technology, some of its current limitations, and a vision of the future.
In Chapter 17, the topic of organismal cloning is described, noting the difference between reproductive and therapeutic cloning. Preformationism and epigenesis (as concepts of development), and the work in the early 1900s that led to the development of the concept of nuclear totipotency, are outlined. As the concept was refined, cells that are pluripotent, multipotent or irreversibly differentiated were described. Cloning using nuclear transfer was first proposed in 1938, and achieved in 1952. More correctly known as somatic cell nuclear transfer (SCNT), the birth of Dolly in 1996 was a milestone in that she was the first mammal to be cloned using a fully differentiated somatic cell as the source of the donor nucleus.
This chapter explores two case histories where American politicians appear to have sided with intense minorities over less-intense majorities. First, I present the case of federal funding for stem cell research in the early 2000s. I find evidence that majorities supported allocating federal health research funds toward research using embryonic stem cells yet federal policy remained stringent for most of the decade. Second, I present the case of firearm regulation following the mass shooting at Sandy Hook Elementary School in 2012. Although large majorities indicated support for new regulation of firearms, no new regulations passed Congress. An intense minority appears to have used costly political action to communicate their strong opposition to new regulations.
The intestinal bulb is a simple dilatation in the anterior part of the intestine of agastric fish. This study was conducted on 18 adult specimens of molly fish (Poecilia sphenops) and demonstrated the presence of an intestinal bulb. The intestinal epithelium was composed of enterocytes covered with microvilli, many mucous goblet cells, and enteroendocrine cells. Numerous intraepithelial lymphocytes, neutrophils, plasma cells, dendritic cells, stem cells, rodlet cells, and macrophages were identified in the epithelial layer. Interestingly, this study recorded the process of autophagy and formation of autophagosomes, multivesicular bodies, and dense bodies. The intestinal epithelium extended into the intestinal gland that consisted of simple columnar epithelium, mucous cells, stem cells, enteroendocrine cells, and basal cells. These glands opened to the lumen of the bulb and were surrounded by a network of telocytes. Moreover, immunohistochemistry revealed that the intestinal epithelium expressed APG5, myostatin, TGF-β, IL-1β, NF-κB, Nrf2, and SOX9. Leukocytes in the lamina propria-submucosa expressed APG5. The inflammatory cells in the connective tissue showed strong immunoreactivity to myostatin and TGF-β. The smooth muscular layer also expressed myostatin. Both IL-1β and NF-κB showed immunoreactivity in macrophages in the lamina propria-submucosa. Stem cells expressed Sox-9 and telocytes expressed NF-κB and SOX9; while astrocytes in the tunica muscularis expressed GFAP. The high frequency of immune cells in the intestinal bulb suggested an immune role of this organ. This is the first study demonstrating the absence of the stomach and its replacement with an intestinal bulb in molly fish, and consequently, this species could be reclassified as agastric fish according to this study.
The construction of governance frameworks for new health technologies is a complex process for most countries, particularly for developing countries. They must grapple with ‘old’ structures and ways of doing things while striving to plant the seeds of the ‘new’, which will put them on a higher level to promote science as well as access to new drugs and treatments. To achieve these goals, international collaboration is a key element. Argentina issued a regulation for advanced therapy medicinal products at the end of 2018. This chapter describes the objectives and actors involved in that process. It focuses on how internal tensions regarding whether to regulate were solved, considering the regulatory harmonisation process promoted by the European Medicines Agency and the US Food and Drug Administration, and the self-regulatory diversification promoted by China and other countries. Special mention is made of the importance of identifying social values and constructing a vision to guide the exercise of ‘foresight’ in law, which resulted in the design and implementation of the new regulation and governance of the system.
Developing tissues have intricate, three-dimensional (3D) organizations of cells and extracellular matrix (ECM) that provide the framework necessary to meet morphogenic and necessary demands. Migrating cells, in vivo, are exposed to numerous conflicting signals: chemokines, ECM, growth factors, and physical forces. While most of these have been studied individually in vivo or in vitro, our understanding of how cells integrate these various signals is lacking. We previously developed a novel self-organizing cellularized collagen hydrogel model that is adaptable, tunable, reproducible, and capable of mimicking the multitude of stimuli that cells experience. Our model produced self-assembled toroids of cells that were formed by 24 h. Data we present here show toroids initially form as early as 3 h after seeding. Additionally, toroids formed when cells were seeded on various collagen subtypes and were sensitive to the composition of the hydrogel. Moreover, we found differences in remodeling in toroid gels compared to gels with cells embedded in them using both a collagen binding peptide and rheology. Using scanning electron microscopy, we observed toroids forming a crater-like structure compared to whole gel contractions in mixed in gels. Finally, when multiple cells were mixed prior to seeding, heterogeneous toroids formed with some containing clusters of cells.
The central nervous system (CNS), consisting of the brain and spinal cord, regulates the mind and functions of the organs. CNS diseases, leading to changes in neurological functions in corresponding sites and causing long-term disability, represent one of the major public health issues with significant clinical and economic burdens worldwide. In particular, the abnormal changes in the extracellular matrix under various disease conditions have been demonstrated as one of the main factors that can alter normal cell function and reduce the neuroregeneration potential in damaged tissue. Decellularised extracellular matrix (dECM)-based biomaterials have been recently utilised for CNS applications, closely mimicking the native tissue. dECM retains tissue-specific components, including proteoglycan as well as structural and functional proteins. Due to their unique composition, these biomaterials can stimulate sensitive repair mechanisms associated with CNS damages. Herein, we discuss the decellularisation of the brain and spinal cord as well as recellularisation of acellular matrix and the recent progress in the utilisation of brain and spinal cord dECM.
Cells in the vocal fold of maculae flavae are likely to be tissue stem cells. Energy metabolism of the cells in newborn maculae flavae was investigated from the aspect of mitochondrial microstructure.
Method
Five normal newborn vocal folds were investigated under transmission electron microscopy.
Results
Mitochondria consisted of a double membrane bounded body containing matrices and a system of cristae. However, these membranes were ambiguous. In each mitochondrion, the lamellar cristae were sparse. Intercristal space was occupied by a mitochondrial matrix. Some mitochondria had fused to lipid droplets and rough endoplasmic reticulum, and both the mitochondrial outer and inner membranes had incarcerated and disappeared.
Conclusion
The features of the mitochondria of the cells in the newborn maculae flavae showed that their metabolic activity and oxidative phosphorylation were low. The metabolism of the cells in the newborn maculae flavae seems to be favourable to maintain the stemness and undifferentiation of the cells.
The availability of new cellular technologies, such as human-induced pluripotent stem cells have opened possibilities to significantly ‘humanise’ the biology of experimental and model organisms in laboratory settings. With greater quantities of genetic sequences being manipulated and advances in embryo and stem cell technologies, it is increasingly possible to replace animal tissues and cells with human tissues and cells. The resulting chimeric embryos and organisms are used to support basic research into human biology. This chapter investigates these transformations in the area of interspecies mammalian chimera. The chapter will explore how human-animal chimeras become objects of regulatory controversy and agreement depending on the concepts, tools and materials used to make them. The final sections of the chapter provide some reflections on the future of chimera-based research for human health, which, as we argue, calls forth a reassessment of regulatory boundaries between human subjects and experimental animals. We argue that interspecies research poses pressing questions for the regulatory structures of biomedicine, especially health research regulation systems’ capacity to simultaneously care for and realign the human and animal vulnerabilities at stake within interspecies chimera research and therapeutic applications.
The traditional notion of the embryo as the developmental phase in which, starting from an undisputable origin (egg, seed) the outline of the bodily architecture of a multicellular organism is shaped, deserves critical discussion. Development does not necessarily have a recognizable starting point. Some of the cells deriving from the zygote may not contribute to the embryo. There are significant differences between the early developmental stages of animals and plants. In animals, at the end of embryonic development the entire structure of the organism is almost always delineated. In plants, the seedling formed during the so-called embryonic development contains only the shoot with the first leaves and the radicle, while the entire structure of the plant, including almost all the leaves and all the flowers, will form from groups of stem cells generated through the entire life of the plant. Development does not necessarily produce an increasing division of labour. Development is not necessarily irreversible. Individual organs are not the products of a distinct developmental process. Differences between species do not always increase progressively from the egg on.
This review assesses regenerative medicine of the upper aerodigestive tract during the first two decades of the twenty-first century, focusing on end-stage fibrosis and tissue loss in the upper airways, salivary system, oropharynx and tongue.
Method
PubMed, Embase, Google Scholar, Cochrane Library, Medline and clinicaltrials.org were searched from 2000 to 2019. The keywords used were: bioengineering, regenerative medicine, tissue engineering, cell therapy, regenerative surgery, upper aerodigestive tract, pharynx, oropharynx, larynx, trachea, vocal cord, tongue and salivary glands. Original studies were subcategorised by anatomical region. Original human reports were further analysed. Articles on periodontology, ear, nose and maxillofacial disorders, and cancer immunotherapy were excluded.
Results
Of 716 relevant publications, 471 were original studies. There were 18 human studies included, within which 8 reported airway replacements, 5 concerned vocal fold regeneration and 3 concerned salivary gland regeneration. Techniques included cell transplantation, injection of biofactors, bioscaffolding and bioengineered laryngeal structures.
Conclusion
Moderate experimental success was identified in the restoration of upper airway, vocal fold and salivary gland function. This review suggests that a shift in regenerative medicine research focus is required toward pathology with a higher disease burden.
What is a stem cell? The answer is seemingly obvious: a cell that is also a stem, or point of origin, for something else. Upon closer examination, however, this combination of ideas leads directly to fundamental questions about biological development. A cell is a basic category of living thing; a fundamental 'unit of life.' A stem is a site of growth; an active source that supports or gives rise to something else. Both concepts are deeply rooted in biological thought, with rich and complex histories. The idea of a stem cell unites them, but the union is neither simple nor straightforward. This book traces the origins of the stem cell concept, its use in stem cell research today, and implications of the idea for stem cell experiments, their concrete results, and hoped-for clinical advances.
The present study aims to investigate the efficacy of intravenously injected mesenchymal stem cells (MSCs) in treating neuropathic pain either before or after its induction by a chronic constriction injury (CCI) model. Rats were divided into four groups: control group, neuropathic group, and treated groups (pre and postinduction) with i.v. mononuclear cells (106 cell/mL). For these rats, experimental testing for both thermal and mechanical hyperalgesia was evaluated. The cerebral cortex of the rats was dissected, and immunohistochemical analysis using anti-proliferating cell nuclear antigen (PCNA), CD117, nestin, and glial fibrillary acidic protein was performed. Our results showed that a single injection of MSCs (either preemptive/or post-CCI) produced equipotent effects on allodynia, mechanical hyperalgesia, and thermal response. Immunohistochemical analysis showed that the stem cells have reached the cerebral cortex. The injected group with MSCs before CCI showing few stem cells expressed PCNA, CD117, and nestin in the cerebral cortex. The group injected with MSCs after CCI, showing numerous recently proliferated CD117-, nestin-, PCNA-positive stem cells in the cerebral cortex. In conclusion, our findings demonstrate that the most probable effect of i.v. stem cells is the central anti-inflammatory effect, which opens concerns about how stem cells circulating in systemic administration to reach the site of injury.
Knowledge and understanding of the appearance of normal bone marrow (BM) and therefore normal haematopoiesis is essential for both general pathologists and specialist haematopathologists. It is only once normal cytology and histology is understood that abnormalities can be identified and defined, leading to the accurate diagnosis of pathologies seen in the BM.
The rapid advance of research in stem cells has opened the door for their potential use in cell-based therapies to treat neurological conditions some of them incurable to date. Encouraging studies in animal models are moving into early phase clinical trials that hold realistic promise for the future. However, important ethical challenges remain as stem cells are translated from preclinical research to the clinical realm.Translation of stem cell–based therapies must be framed within a rigorous scientific and ethical process. This framework extends to the continuum of basic science in the laboratory, subsequent animal studies to the execution of early and late phase clinical trials in humans.Neurosurgery will play a fundamental role in the stem cell therapies of the future. New neurosurgical techniques and instruments will be developed for the delivery of stem cells to single or multiple targets within the CNS. Neurosurgeon’s roles will expand as stem cells move from clinical trials to effective potential therapies. This chapter will review selected stem cell ethical issues, that may inform and guide the practicing neurosurgeon in a rapidly moving field of great scientific promise, as well as ethical challenges
In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide.