Biological Sciences
Stem Cells
Stem cells are undifferentiated cells with the unique ability to develop into different types of cells in the body. They can divide and renew themselves over long periods, serving as a repair system for the body. Stem cells are of great interest in biological research and medical applications due to their potential to treat a wide range of diseases and injuries.
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11 Key excerpts on "Stem Cells"
eBook - PDFGene and Cell Therapy
Therapeutic Mechanisms and Strategies, Fourth Edition
- Nancy Smyth Templeton(Author)
- 2015(Publication Date)
- CRC Press(Publisher)
743 28 28.1 INTRODUCTION Stem cell biology has become a flourishing field. In order to meet the classical definition of a stem cell, a cell must have two properties: self-renewal and potency. Self-renewal is the ability of a stem cell to replicate itself by dividing into the same nonspecialized cell type over long periods. This prop-erty ensures the maintenance of a pool of Stem Cells. In order to self-renew, Stem Cells could go through two different types of cell division: one is asymmetric division, in which a stem cell divides into a differentiated cell and a stem cell; the other one is symmetric division, in which the daughter cells are both Stem Cells. Potency is defined as a stem cell’s potential to differentiate into more specialized cells. There are many types of Stem Cells, which can be classified based on their potency. The greater the ability of a stem cell to differenti-ate into more and diverse cell types, the greater its potency. Totipotent Stem Cells, which differentiate into all cell types in an organism and in extra-embryonic tissues, are the most potent. The zygote and the cells derived from its first few divi-sions are considered to be totipotent. Pluripotent Stem Cells rank second by having the potency to differentiate into all cell types in three embryonic germ layers: endoderm, meso-derm, and ectoderm. Multipotent, bipotent, and unipotent are terms applied to Stem Cells with the potential to differentiate into several, two, and single cell types, respectively. Stem Cells can also be classified according to their origins or functions as follows. Those derived from early embryos are called embryonic Stem Cells (ESCs); those that exist in adult organisms are called adult Stem Cells. There are many types of adult Stem Cells, such as mesenchymal Stem Cells, hematopoietic Stem Cells (HSCs), spermatogonial Stem Cells, adipose-tissue-derived Stem Cells, and skin Stem Cells. In general, adult Stem Cells exhibit a more restricted potency than ESCs.
eBook - ePubStem Cells
Therapeutic Innovations under Control
- Nicole Arrighi(Author)
- 2018(Publication Date)
- ISTE Press - Elsevier(Publisher)
1Definition and Classification of Stem Cells
Abstract
Stem Cells are the original cells of the human being. With infinite multiplication potential and the ability to differentiate into any type of cell of the organism, Stem Cells are the foundations of tissues, organs and the entire organism. Throughout life, they regenerate and repair damaged tissues following injury or illness. Amplified from a sample taken from the patient or genetically modified, these cells grafted onto a support guarantee an optimal anchoring and a rapid proliferation. This living graft, transplanted onto the damaged tissue area, is capable of introducing cells that restore its function. These Stem Cells form the basis of the tissue repair processes. But what is a stem cell? Where does it come from? Where in the organism is it located? What is its role?Keywords
Bone-marrow Stem Cells; Cardiac muscle Stem Cells; Cell lineage; Fertilization; Intestinal Stem Cells; Neural Stem Cells; Pluripotent embryonic Stem Cells; Skeletal muscle Stem Cells; Skin Stem Cells; Umbilical cord blood Stem Cells“I was captivated by the idea of understanding and controlling the pluripotent state”.(Austin Smith, Director of the Wellcome Trust Centre for Stem Cell Research , Cambridge)Stem Cells are the original cells of the human being. With infinite multiplication potential and the ability to differentiate into any type of cell of the organism, Stem Cells are the foundations of tissues, organs and the entire organism. Throughout life, they regenerate and repair damaged tissues following injury or illness. Amplified from a sample taken from the patient or genetically modified, these cells grafted onto a support guarantee an optimal anchoring and a rapid proliferation. This living graft, transplanted onto the damaged tissue area, is capable of introducing cells that restore its function. These Stem Cells form the basis of the tissue repair processes. But what is a stem cell? Where does it come from? Where in the organism is it located? What is its role?
eBook - PDF- Charles Durand, Pierre Charbord(Authors)
- 2021(Publication Date)
- River Publishers(Publisher)
Historically, the term Stem Cells was first coined to refer to the fertilized egg, from which all the cells of the organism stem (Maehle, 2011; Lancaster, 2017). Now 27.3 Self-Renewal and Differentiation Definition 687 several scientists argue that the concept would gain clarity if these early mammalian embryonic cells where not referred to as Stem Cells. In other species, though, these pluripotent cells can remain throughout the life of the organism and are thus called Stem Cells (Lai and Aboobaker, 2018), like neoblasts in planarians (Zeng et al., 2018). How different are these planarians pluripotent Stem Cells/ neoblasts from the pluripotent (non-stem) cells of mammalian embryo? Are the biological differences between them sufficient to support that the former are considered Stem Cells while the latter are not? In addition, assessing self-renewal ability might not always be easy. For example, there is a debate on how much hematopoietic Stem Cells (HSCs) actually self-renew during the life of an organism. Using mouse models that allow cell division tracking, some have argued that HSCs only divide four times before they enter permanent senescence (Bernitz et al., 2016; see also Wilson et al., 2008). Others have highlighted a great diversity among HSCs, suggesting that each “individual HSCs possess an almost unique capability to self-renew” (Haas et al., 2018), and among which some might never divide (and thus self-renew) during the adulthood (Morcos et al., 2020). How much should a cell self-renew to be considered a stem cell? Stem cell definition thus faces three problems: (1) the name refers to cells that can vary greatly in their abilities to self-renew and to differentiate, (2) these two properties are unspecific and (3) the difference between Stem Cells and non-Stem Cells might be more quantitative than qualitative.
eBook - PDF- Jonathan M. W. Slack(Author)
- 2017(Publication Date)
- Wiley-Blackwell(Publisher)
Moreover, understanding stem cell behavior means understanding various aspects of cell and developmental biology which are not always familiar to workers in stem cell laboratories. The above definition is of value in indicat-ing the special characteristics of stem cell 1 What is a Stem Cell? The Science of Stem Cells 2 behavior, but is also helpful in indicating what is not stem cell behavior. For example, most of the cells in the body that are dividing are not Stem Cells. In particular cells in the embryo that differentiate after a certain period of time, such as the earliest cells formed by division of the fertilized egg, are not Stem Cells. Nor are differentiated cells that divide during postnatal life to generate more of themselves, such as hepatocytes or tissue‐resident macrophages. A common term found in the literature is “stem/progeni-tor cell”. This is a singularly unhelpful desig-nation as it conflates two entirely different cell behaviors. Progenitor cells are precisely those that differentiate into functional cell types after a finite period of multiplication. They include the transit amplifying cells that arise from Stem Cells (Figure 1.1) and also cells of the embryo and of the growing indi-vidual that are destined to differentiate after a certain time. Real Stem Cells comprise two fundamen-tally different types: pluripotent Stem Cells that exist only in vitro, and tissue‐specific Stem Cells that exist in vivo in the postnatal organism. Pluripotent Stem Cells comprise embryonic Stem Cells (ESC) and induced pluripotent Stem Cells (iPSC). There are vari-ous subdivisions that will be considered later, but the essential features of these cells are first that they can be propagated without limit in vitro, and second that, under appro-priate culture conditions, they are able to give rise to a wide variety of cell types, per-haps all the cell types in the normal organism except for the trophectoderm of the placenta.
eBook - PDF- Kay Elder, Brian Dale(Authors)
- 2020(Publication Date)
- Cambridge University Press(Publisher)
Unipotent cells, such as spermatogonial Stem Cells, are self-renewing cells that have the potential to give rise to a single lineage, spermatogonia. Figure 7.1 illustrates a hier- archy of stem cell potential. Two properties are unique to all types of stem cell: 1. They have the capacity for long-term self-renewal. 2. They have the potential to give rise to cells other than themselves. A stem cell line is a population of cells that has been grown and maintained in vitro. When maintained under appropriate conditions, these cells continue to grow in tissue culture for very long periods of time. Mammalian Stem Cell Lines Following the derivation and culture of human embryonic stem cell lines in the late 1990s (Thomson et al., 1998), debate and controversy escalated 135 surrounding the use of surplus human embryos donated for research. Despite the controversial ethico-legal perspectives, in many countries through- out the world IVF clinics have embryos that are either unsuitable for treatment or are surplus to the patient’s requirements. Given the opportunity for appropriate counseling and informed consent, many patients choose to make a contribution to science by donating surplus embryos for research rather than allowing them to perish (Franklin et al., 2008). There is no doubt that embryos donated for stem cell research represent a very valuable resource for scientific investigation, with the potential to make a significant contribution to our understanding of early develop- mental processes and the molecular pathology of dis- ease. Stem cell biology has become an integral part of ART; the principles and the science underpinning this new area of developmental and regenerative biology Restriction Totipotent non-self-renewing Pluripotent self-renewing Broad potential self-renewing Limited potential limited self-renewal Limited division non-functional Non-mitotic functional Neuron, cardiomyocyte hepatocyte, etc.
eBook - PDF- Bruce M. Carlson, Bruce M. Carlson(Authors)
- 2011(Publication Date)
- Academic Press(Publisher)
In the case of the liver, for example, the backup system can act at several levels. The first level is the parenchyma. The second level is the oval cells, which represent a local progenitor population. A third level of compensation may be Stem Cells originating from outside the organ itself. WHAT IS A STEM CELL? Much of our knowledge of Stem Cells comes from the numerous studies on the hema-topoietic system, which serves as a model, although not necessarily the only one, for understanding the properties and capabilities of Stem Cells (Körbling and Estrov, 2003; Weissman, 2000). Even in this well-studied system, many major questions remain. A generic definition for Stem Cells is “self-renewing populations of cells that undergo symmetric and asymmetric divisions to self-renew or differentiate into multiple kinds of differentiated progeny” (Cai et al., 2004, p. 585). Many different types of Stem Cells currently have been identified. The first dichot-omy in a classification of Stem Cells is between embryonic (ES) and adult Stem Cells. ES cells are derived from the inner cell mass of blastocysts. These have been described as totipotent because a single cell from the inner cell mass can, in theory, go on to form any of the differentiated cell types in the body. Permanent cell lines derived from Stem Cells, Plasticity, and Regeneration 241 single ES cells can be perpetuated in vitro. From such founder lines, subsets of cells can be exposed to defined culture conditions and steered to differentiate along certain specific pathways before being implanted into damaged or deficient tissues of organs. This seemingly straightforward approach shows great promise, but it is fraught with technical difficulties. In addition to understanding how to direct the ES cells toward differentiation in a desired direction, other important issues are the potential develop-mental lability of these cells and their antigenicity.
eBook - PDFFreshney's Culture of Animal Cells
A Manual of Basic Technique and Specialized Applications
- Amanda Capes-Davis, R. Ian Freshney(Authors)
- 2021(Publication Date)
- Wiley-Blackwell(Publisher)
Guidelines are also available that set out the fundamental principles and standards required for stem cell research and clinical translation (ISSCR 2016). Freshney’s Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications , Eighth Edition. Amanda Capes-Davis and R. Ian Freshney. © 2021 John Wiley & Sons Ltd. Published 2021 by John Wiley & Sons Ltd. Companion website: www.wiley.com/go/freshney/cellculture8 23.1 TERMINOLOGY: Stem Cells Stem cell terminology often varies between publications and can be quite confusing. Logically, this is not surprising. Stem Cells vary in their characteristics depending on their origin and the type of characterization that is performed. They also tend to be studied in different areas of specialization, resulting in inconsistent reporting. Some journals and organizations have developed glossaries or position statements on stem cell terms, which help to provide a consensus approach (Smith 2006; ISSCR 2016; NIH 2019b). Where a consensus has not been developed, the simplest approach is to describe Stem Cells in accordance with their source and potency (see Section 2.4.2) (Ilic and Polak 2011). Stem Cells can be isolated from many different sources, which all have advantages and disadvantages for research and clinical applications (see Table 23.1). Stem Cells from various sources can be broadly divided into (i) prenatal Stem Cells, which include embryonic Stem Cells (ESCs) from the pre-implantation embryo; (ii) perinatal Stem Cells from tissues such as the amniotic fluid, placenta, and umbilical cord; (iii) postnatal Stem Cells (often described as adult Stem Cells), which include HSCs and other cell types that give rise to spe-cific lineages; (iv) reprogrammed Stem Cells, which have been manipulated in vitro to increase their level of potency; and (v) disease-related Stem Cells, which are capable of self-renewal and differentiation but where regulation of these processes may be aberrant.
- David C. Hay(Author)
- 2012(Publication Date)
- CRC Press(Publisher)
22 Regenerative Medicine, Stem Cells and the Liver the blastocyst are pluripotent and become an embryo proper composed of cells of all three germ layers. Multipotent Stem Cells are more restricted in their differentiation potential and are committed to differentiate into cells within a particular tissue type (Wagers and Weissman 2004). Due to their self-renewing and differentiation potential, Stem Cells are considered as cellular resources for the treatment of several disorders that come as a result of disease or injury. As such, their role in regeneration is the subject of extensive research. In this chapter, we will review the potential of pluripotent Stem Cells for regenerative medicine (Fig. 3.1). We will first discuss the therapeutic potential of embryonic Stem Cells (ESCs) and provide an overview of methods for cellular reprogramming. Progress in the experimental and clinical applications of Stem Cells in regenerative medicine will be discussed. Challenges that need to be overcome to make stem cell-based therapy will be addressed. Figure 3.1. Overview of the step-wise application of pluripotent Stem Cells in regenerative medicine. Self-renewal and pluripotency render pluripotent ESCs or iPSCs as important cells for regenerative medicine. Somatic cells isolated from patients (Step 1) are to be reprogrammed via genenetic or non-genetic approach (Step 2). Reprogrammed iPSCs are in vitro differentiated into cells of interest (Step 3), which are used for the transplantation as autologous cells for the patients (Step 4). Role of Pluripotent Stem Cells in Regenerative Medicine 23 Embryonic Stem Cells and their uses ESCs are the in vitro derivatives of the inner cell mass of the blastocyst. ESCs have the attributes of self-renewal and pluripotency. The first ESC lines were established from mouse blastocysts in 1981 (Evans and Kaufman 1981, Martin 1981).
eBook - PDFCancer Stem Cells
Philosophy and Therapies
- Lucie Laplane(Author)
- 2016(Publication Date)
- Harvard University Press(Publisher)
Generic definition E.g.: Stem Cells are the cells from which tissues develop and maintain. SC subtype C SC subtype A SC subtype B Sub-subtype 1 Sub-subtype 2 Specific definition Property a Property a Property b Property a Property b Property c Property c Property d Property c Property d Property d Property e 114 D E B A T E S O N C S C S A N D S T E M C E L L S S T E M C E L L I D E N T I T Y 115 tinguish the diverse subtypes of pluripotent Stem Cells, such as embry-onic Stem Cells and induced pluripotent Stem Cells, and the subtypes of the multipotent Stem Cells, such as hematopoietic Stem Cells, intestinal Stem Cells, or germinal Stem Cells. And it would also distinguish such sub-subtypes among species, acknowledging the differences between human and mouse hematopoietic Stem Cells, for example. M O L E C U L A R S I G N AT U R E In the early 2000s, three groups independently tried to identify a “stem-ness signature,” i.e., a cluster of genes that would be overexpressed in different kinds of Stem Cells compared to non-Stem Cells. This research relied on two assumptions: A1. Stemness (self-renewal and differentiation) qualitatively distin-guishes Stem Cells from non-Stem Cells. A2. Stemness is reducible to a set of molecular properties (gene transcripts, cell surface proteins, etc.). These assumptions rely on the idea that “because all Stem Cells share fundamental biological properties, they may share a core set of molec-ular regulatory pathways” (Ivanova et al. 2002, 601). A1 faces the critiques highlighted in the previous section. On one hand, self-renewal and differentiation are not specific to Stem Cells. On the other hand, certain Stem Cells express only one of the two proper-ties. Thus, even if A2 is correct, a molecular definition of stemness would not allow a distinction between Stem Cells and non-Stem Cells. Molecular data tend to confirm this diagnosis at several levels.
eBook - PDFUmbilical Cord Blood
A Future for Regenerative Medicine?
- Suzanne Kadereit, Gerald Udolph;;;(Authors)
- 2010(Publication Date)
- WSPC(Publisher)
267 INTRODUCTION Embryonic Stem Cells, e.g., Stem Cells derived from the inner cell mass of early embryos, have received much attention due to their pluripotency and unlimited self-renewal potential. 1 To date, however, these cells have not been translated into the clinic. In contrast, adult-derived cells such as mesenchymal cells derived from the bone marrow, have clinical value, despite their limited self-renewal ability and limited differentiation potential. 2–7 Contrary to embryonic Stem Cells, many clinical trials are on-going for adult-derived cells, and for some adult-derived cells clinical use is already a routine. 8 One problem ascribed to cell therapies derived from adult tissues is cell collection which may involve hospitalization and a painful, invasive procedure for the donor. Additionally, there may be a waiting period for locating the donor and arranging for the collection. Other problems are that the cells must be isolated and expanded using established good tissue manufacturing practices (GMP). However, adult-derived cells have limited expansion ability in vitro and require tissue matching to avoid rejection and to limit graft versus host disease (GVHD). Cryogenic stability is another concern with adult-derived therapeutic cells. 9 These problems are significant barriers preventing extensive cell banking for adult-derived therapeutic cells. The ability to bank cells for therapeutic use is a prerequisite for off-the-shelf cell therapy to produce commercial success and a reason for consideration of umbilical cord blood or Wharton’s jelly-derived mesenchymal stromal cells for cellular therapies. One appealing aspect of umbilical cord-derived cells and tissue is the fact that it is derived from a fetal deciduous tissue, e.g., a tissue rendered superfluous at birth. The collection of blood and cells from discarded fetal tissue is free of ethical controversy.
eBook - PDF- Julia M Polak, Sakis Mantalaris, Sian E Harding(Authors)
- 2008(Publication Date)
- ICP(Publisher)
Stem Cells 25 (2), 364–370 (2007). 34. Le Blanc, K. and Pittenger, M. Mesenchymal Stem Cells: progress toward promise. Cytotherapy 7 (1), 36–45 (2005). 35. Le Blanc, K. Mesenchymal stromal cells: tissue repair and immune modula-tion. Cytotherapy 8 (6), 559–561 (2006). 36. Fibbe, W.E., Nauta, A.J. and Roelofs, H. Modulation of immune responses by mesenchymal Stem Cells. Ann. N. Y. Acad. Sci. 1106 , 272–278 (2007). 37. van Laar, J.M. and Tyndall, A. Adult Stem Cells in the treatment of autoim-mune diseases. Rheumatology ( Oxford ) 45 (10), 1187–1193 (2006). 38. Uccelli, A., Moretta, L. and Pistoia, V. Immunoregulatory function of mes-enchymal Stem Cells. Eur. J. Immunol. 36 , 2566–2573 (2006). 39. Koch, C.A., Geraldes, P. and Platt, J.L. Immunosuppression by embryonic Stem Cells. Stem Cells 26 , 89–98 (2008). 213 Stem Cell Immunology This page intentionally left blank This page intentionally left blank 215 Chapter 11 Development of a Design of Experiment Methodology: Applications to the Design and Analysis of Experiments Mayasari Lim and Athanasios Mantalaris Abstract Stem cell cultures are complex and intricate processes. There are many con-tributing factors that affect and influence the outcome of the culture, including (1) factors affecting the physicochemical environment, (2) nutrients and metabolites, (3) growth factors, and (4) the various cell types that exist within the cell culture system, as shown in Fig. 1A. 1–8 Physicochemical factors, such as pH, temperature, dissolved oxygen and carbon dioxide levels, determine the cellular environment and affect cellular behaviour and functionality. Slight changes in the levels of these physicochemical parameters will result in large changes in the cellular output. For instance, the optimal pH for the process of megakaryopoiesis in haematopoietic cell cultures has been reported to be at pH 7.60 while for the process of granulopoiesis it has been reported to be at pH 7.21.
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