Biology and Engineering of Stem Cell Niches

Ajaykumar Vishwakarma, Jeffrey M Karp

• Publisher: Academic Press
• Year: 2017
• Print ISBN: 9780128027349
• eBook ISBN: 9780128027561
• Topic: Scienze biologiche
• Subtopic: Biotecnologia

Biology and Engineering of Stem Cell Niches covers a wide spectrum of research and current knowledge on embryonic and adult stem cell niches, focusing on the understanding of stem cell niche molecules and signaling mechanisms, including cell-cell/cell-matrix interactions.The book comprehensively reviews factors regulating stem cell behavior and the corresponding approaches for understanding the subsequent effect of providing the proper matrix molecules, mechanical cues, and/or chemical cues. It encompasses a variety of tools and techniques for developing biomaterials-based methods to model synthetic stem cell niches in vivo, or to enhance and direct stem cell fate in vitro.A final section of the book discusses stem cell niche bioengineering strategies and current advances in each tissue type.- Includes the importance of Cell-Cell and Cell Matrix Interactions in each specific tissue and system- Authored and edited by authorities in this emerging and multidisciplinary field- Includes valuable links to 5-10 minute YouTube© author videos that describe main points

Part I

Biology of Stem Cell Niches and Molecular Mechanisms

Outline

Chapter 1. The Need to Study, Mimic, and Target Stem Cell Niches

Chapter 2. Harnessing the Biology of Stem Cells' Niche

Chapter 3. Pluripotent Stem Cell Microenvironment

Chapter 4. Regulation of Hematopoietic Stem Cell Dynamics by Molecular Niche Signaling

Chapter 5. HSC Niche: Regulation of Mobilization and Homing

Chapter 6. Neuronal Stem Cell Niches of the Brain

Chapter 7. Cardiovascular Stem Cell Niche

Chapter 8. Intestinal Epithelial Lgr5+ Stem Cell Niche and Organoids

Chapter 9. The Epithelial Stem Cell Niche in Skin

Chapter 10. The Satellite Cell Niche in Skeletal Muscle

Chapter 11. The Cancer Stem Cell Niche

Chapter 12. Cellular Senescence and Stem Cell Niche

Chapter 1

The Need to Study, Mimic, and Target Stem Cell Niches

Ajaykumar Vishwakarma^1,2, Jeroen Rouwkema^1,2,3, Peter Anthony Jones^1,2,4, and Jeffrey M. Karp^{1,2,4 1}Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, United States ²Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States ³University of Twente, Enschede, The Netherlands ⁴Harvard Stem Cell Institute, Cambridge, MA, United States

Abstract

Despite important advances in tissue repair and regeneration over the past few decades, complete functional repair of damaged or diseased human tissues has remained elusive. Recent discoveries in stem cell niche molecular biology and biomaterials engineering may hold the key to true regeneration. Such efforts can be divided into three main approaches: (1) recruiting endogenous repair mechanisms in vivo, (2) administering cells in vivo, and (3) generating tissues/organs ex vivo. Central to these approaches is an understanding of stem cell niche molecules and signaling mechanisms, including cell–cell and cell–matrix interactions. To better study these mechanisms, scientific research has focused on the creation of a synthetic or artificial niche, a two- or three-dimensional microenvironment, constituted by the integration of mechanical and chemical cues such as extracellular matrix molecules and growth factors. This book is an attempt to comprehensively review our current understanding of the biology of the stem cell niche. It covers the elements that regulate stem cell behavior and highlights a variety of tools and techniques available in engineering and materials science for modeling synthetic stem cell niches in vivo or enhancing and directing stem cell fate in vitro. Finally, it describes stem cell niche bioengineering strategies and current advances in each tissue type.

Keywords

Cell–cell interaction; Cell–matrix interaction; Extracellular matrix; Microenvironment; Stem cell niche; Tissue regeneration; Tissue repair

Outline

1. Introduction

1.1 The Stem Cell Niche in Health and Disease

1.2 Components of Stem Cell Niche

2. Biology of the Stem Cell Niche

2.1 Behavior of Stem Cells: Hierarchical Versus Stochastic Model

2.2 Embryonic and Adult Stem Cell Niches

3. Biochemical and Biophysical Regulation of Stem Cell Behavior

3.1 Extracellular Matrix and Biochemical Cues

3.2 Soluble Growth Factors and Ligands

3.3 Physical Cues and Matrix Mechanics

3.4 Oxygen and Metabolism

3.5 Immune Cells, Inflammation, and Immunomodulation

4. Mimicking the Stem Cell Niche: Bioengineering Tools and Techniques

5. Bioengineering Specialized Artificial Stem Cell Niches for Clinical Therapies

References

1. Introduction

1.1. The Stem Cell Niche in Health and Disease

As opposed to single-celled organisms, cells in complex multicellular organisms are associated with a tissue-specific physiological environment. Different cell types differ in morphology and function; yet, they are genetically identical. This variation, caused by differential gene expression, is controlled by intrinsic mechanisms and by extrinsic signals from the local environment, thereby controlling distinct cellular behavior, or “phenotype.” The local physiological microenvironment supporting the cell and driving extrinsic cues from outside the cell is known as the “cell niche,” which is composed of extracellular matrix (ECM) components for attachment/anchorage, diffusible biomolecules for cell signaling, cell surface ligands for signal transduction, and essential cell–cell interactions.

Studies of cell populations during embryonic development have led to the identification of stem cells that possess the capacity to produce a full organism from a fertilized egg.¹ Stem cells are functionally defined as undifferentiated embryonic or adult cells, which can self-renew and generate differentiated cell types with varying degrees of potency. The fundamental replicative feature of stem cells, along with their generation of differentiated progeny, accounts for the origin of the word “stemness.” However, whether stem cells need a special environment that controls stem cell renewal, maintenance, and survival, and what is the nature of such microenvironment are pertinent questions many researchers continue to explore. With growing evidence, there is a growing consensus that in vivo function and the fate of stem and progenitor cells are regulated by the interplay of various extrinsic signals of tissue-specific microenvironments, often referred to as “stem cell niches.”

The concept of a stem cell niche was first proposed by Schofield in the late 1970s as a physiologically restricted microenvironment that supports stem cells.² The initial concept of anatomically distinct sites that regulate hematopoietic stem cell (HSC) activity and self-renewal was later extended to acknowledge the discovery of stem cells and their niches in multiple tissues.³ Stem cells are often linked with asymmetrical cell division, and the niche maintains a stable number of stem cells during homeostasis, and removal of the niche induces differentiation. Extrinsic signals interact and integrate to ensure that one cell remains in the niche, while another escapes it by receiving a differentiation signal. It is now clear that in high-turnover systems, such as in the gut and blood, the behavior of stem cells is not uniformly quiescent, and the various niche components may govern their relative proliferative activity.^4–6 Also, it is emerging that stem cell performance is not only dependent on factors promoting stemness but is also a result of factors inhibiting differentiation pathways. Hence, in homeostasis, the underlying relationship between stem cell and niche accommodates nuances and involves various elements influencing the stem cell functional parameters: replicative capacity and potency. However, when tissue is injured or diseased, the niche actively engages stem cells; guides their proliferation, migration, and differentiation; and regulates their participation in tissue regeneration and repair. Therefore, the niche should be regarded as a dynamic participant controlling stem cell number, fate, and behavior in the health and disease of the tissue and the organism.

1.2. Components of Stem Cell Niche

The stem cell niche is a complex, heterotypic, and dynamic structure, which includes supporting ECM, neighboring niche cells, secreted soluble signaling factors (such as growth factors and cytokines), physical parameters (such as shear stress, tissue stiffness, and topography), and environmental signals (metabolites, hypoxia, inflammation, etc.) (Fig. 1.1).^7,8 Stem cell niches are highly innervated and densely vascularized, thus are directly or indirectly influenced by vascular and neural inputs.

Figure 1.1 Components of stem cell niche. Adapted from Lane SW, Williams DA, Watt FM. Modulating the stem cell niche for tissue regeneration. Nat Biotechnol 2014;32(8):795–803.

In addition to matrix and cell signaling elements mentioned above, niche cells form functional units within the stem cell niche. These are neighboring tissue-specific stem or s...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Foreword
• Part I. Biology of Stem Cell Niches and Molecular Mechanisms
• Part II. Biochemical and Physical Cues in The Stem Cell Niche Directing Cell Fate
• Part III. Designing Smart Biomaterials to Mimic and Control Stem Cell Niche
• Part IV. Bioengineering Strategies to Model Synthetic Stem Cell Niches
• Index