Stem Cells

Therapeutic Innovations under Control

Nicole Arrighi

• Publisher: ISTE Press - Elsevier
• Year: 2018
• Print ISBN: 9781785482540
• eBook ISBN: 9780081025888
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

Stem Cells: Therapeutic Innovations under Control traces the discovery of stem cells and induced pluripotent cells. It establishes the link between knowledge about cell development and tissue engineering, and presents perspectives in regenerative medicine. Cell proliferation and tissue architecture open up unexpected applications in tissue engineering, with the development of tissues or organs. In this context emerges the need to address the issue of bioethics and regulatory considerations. Because stem cells can multiply and differentiate into cells specific to a particular tissue or organ, they represent vast potential in the health field.- Traces the discovery of stem cells to link knowledge of cell development with tissue engineering- Presents prospects in regenerative medicine- Establishes the link between knowledge about cell development and tissue engineering

1

Definition 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?

The aim of this chapter is to define the unique properties of stem cells (SCs), locate their source and understand their development. In the human organism, several categories of SCs exist; this chapter is organized into three parts corresponding to the three categories of stem cells.

First, the stem cells present in the various tissues of the human organism will be addressed. These are called adult stem cells and are located in specific tissues or organs, part of the adult organism. Bone-marrow-, muscle-, skin- and adipose tissue-derived SCs as well as their physiological functions and the molecular markers that characterize them are thus presented. All SCs of the tissues or organs of the organism have a common origin: they come from SCs of the embryo. Each of the embryonic SCs can give rise to an entire organism. Second, in section 1.3, we will examine these embryonic SCs, situating the early stages of the embryo’s development and their role in the first weeks after fertilization. Finally, section 1.4 presents the discovery that has given a boost to regenerative medicine: the reprogramming of somatic cells into induced pluripotent cells. As if they were going back in time to the embryonic stage, these stem cells again become pluripotent and cover potentialities close to those of embryonic SCs. Sampled from the adult individual and not from the embryo, they pave the way for tissue regeneration therapies, which could have been restrained by the ethical constraints linked to embryonic SCs.

1.1 Two characteristics specific to stem cells

SCs are original cells that are considered to be the progenitors of more than 200 types of cells in the human body. They are able to divide and produce other cells that can become highly specialized. Cells are said to be SCs if they possess the following two characteristic properties: self-renewal and pluripotency. Self-renewal is the ability to multiply infinitely, by simple division. Pluripotency means that the cell is capable of producing all of the organism’s cell types. These properties can be demonstrated in vitro where the progeny of the SCs is characterized by the expression of specific genes of a cell lineage. This process is called differentiation.

Thanks to the aforementioned two properties, SCs continually reconstitute the organism’s stock of cells. They assure the renewal of the cells, which have different lifecycles. While the intestine cell is renewed after 5 days and that of the retina after 10 days, other cells live longer, such as the red blood cell, which is renewed after 120 days, or the liver cell, which lives for approximately 400 days. The subject of cancerous cells will intentionally not be discussed in this book. Although they present an infinite multiplication, they do not, however, have the capacity to generate all of the tissues of the organism.

1.1.1 An infinite multiplication capacity: self-renewal

The future for SCs – self-renewal or differentiation – is determined through the process of cell division. SCs produce undifferentiated SCs or specialize into progenitor cells. This process is regulated by symmetric and asymmetric divisions. It depends on cell-intrinsic and cell-extrinsic factors, such as microenvironmental stimuli. It is then possible for the signals from a specific microenvironment to be able to control SC dynamics. For example, SCs with a wide differentiation potential exist in bone marrow. SCs are also located in the tissues or in niches that provide a specific cellular environment indispensable for unlimited renewal.

Symmetric division gives rise to two identical daughter cells possessing the properties of the SCs. Asymmetric division produces an SC and a progenitor cell with limited self-renewal potential. The progenitors can perpetuate several cycles of cell division before finally differentiating into a specialized cell. The molecular differences between symmetric and asymmetric division would be based on a differential selection of membrane proteins (receptors) between the daughter cells. The SC continuously generates daughter cells that are invariably identical to it and, in parallel, generates other daughter cells that have different, more restricted properties.

The capacities for self-renewal and specialization are inverse. The SC is not specialized and possesses maximum self-renewal capabilities. Through the process of differentiation, it produces the progenitors and then the precursors, which is the last step toward the production of the specialized cell. This differentiated cell has lost its self-renewal capability; however, its specificity is maximum.

SCs can differentiate into several cell types, and this broad range of differentiation orientations is called SC plasticity. They have the ability to move from one type of differentiated cell to another, that is, transdifferentiation.

Figure 1.1 Self-renewal of SCs and progenitor cells. Symmetric division produces two identical cells, whereas asymmetric division leads to two different cells. For a color version of this figure, see www.iste.co.uk/arrighi/stemcells.zip

1.1.2 A specialization ability: differentiation

The organism’s original SCs are present in the fertilized egg, also known as the zygote. The zygote is a cell resulting from the fusion of two gametes. At this first stage in development, the fertilized egg possesses all differentiation capacities. The cells, which compose it, are called totipotent, from the Latin totus, meaning “everything”. They are fit for everything in the sense that they have the ability to become a complete individual. They can form an embryo, as well as the placenta. The egg divides into two, four and then eight cells. After 4 days, the egg resembles a blackberry and hence this stage is named morula, meaning “blackberry” in Latin.

After 5–6 days, the embryo reaches the stage of blastocyst, from the Greek blastos, meaning ‘bud”. It takes the form of a hollow ball and consists of approximately 200 cells. The peripheral cells, or trophectoderm, will form the placenta, necessary for embryonic implantation. Inside this ball are approximately 30 cells, from which more than 200 different cell types of the organism can develop. This internal cellular mass contains SCs that are pluripotent, from the Latin pluris, which means “the most”, in the sense of a larger quantity. They can diversify into any tissue of the organism, but they are unable to produce a complete individual. Pluripotent cells produce three embryonic layers, namely the endoderm, the mesoderm and the ectoderm. Each layer generates determined cells for each organ.

The embryonic layers contain cells that are multipotent, from the Latin prefix multi, which means “many”. They are capable of diversifying into a limited number of cell types with the same embryonic origin.

Each layer generates determined cells for each organ or line, known as unipotent SCs. They undergo a unique lineage that enables the production of a specific cell type.

Figure 1.2 The fate of SCs from the totipotency of the egg to the pluripotent cells of the embryo, then multipotent cells of the embryonic layers and finally specific cells of each organ of the human body. For a color version of this figure, see www.iste.co.uk/arrighi/stemcells.zip

The SCs present in the human body are multipotent or unipotent. They do not exhibit any specialized physiological property. They are categorized into the following three large families, whose characteristics and locations are different:

• – Embryonic SCs, or ES (embryonic stem) cells, are derived from the human embryo a few days after fertilization. The embryo is in the early stages of its development; it is not yet implanted, hence the term “preimplantation embryo”. At this stage, it contains a compact mass of cells, known as inner cell mass, which are the pluripotent embryonic SCs.
• – The adult or tissue-specific SCs are located in the tissues and organs of the human body, yet in minimal amounts. They are responsible for tissue renewal, differentiating into any specialized cell type of the tissue or organ. Their primary role is to maintain and repair the tissue where they are located, s...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Acknowledgments
• Introduction
• 1: Definition and Classification of Stem Cells
• 2: Stem Cells as a Necessary Experimental Platform in Medical Research
• 3: Stem Cells at the Core of Cell Therapy
• 4: Stem Cells for Regenerative Medicine in Humans
• 5: Bioethics: Regulatory Framework for Human Stem Cells
• Glossary
• Bibliography
• Index