Preface

Chapter 8 **A Vascular Perspective on Neurogenesis 199** Joshua S. Goldberg and Karen K. Hirschi

Roberta Parolisi and Maria Armentano

**Section 3 Neural Stem Cells and Regenerative Medicine 269**

Chapter 10 **A Survey of the Molecular Basis for the Generation of**

**Inflammatory CNS Disorders 287**

Chapter 13 **Neuroinflammation on the Epigenetics of Neural**

Nando Dulal Das and Young Gyu Chai

Olivier Liard and Emmanuel Moyse

**Structural Plasticity 241**

**Medicine 271**

Takahashi

**VI** Contents

Shan Bian

**Stem Cells 381**

**Cell Therapy 397**

Chapter 9 **Parenchymal Neuro-Glio-Genesis Versus Germinal Layer-**

**Derived Neurogenesis: Two Faces of Central Nervous System**

Luca Bonfanti, Giovanna Ponti, Federico Luzzati, Paola Crociara,

**Functional Dopaminergic Neurons from Pluripotent Stem Cells:**

Kaneyasu Nishimura, Yoshihisa Kitamura, Kiyokazu Agata and Jun

Matteo Donegà, Elena Giusto, Chiara Cossetti and Stefano Pluchino

**Insights from Regenerative Biology and Regenerative**

Chapter 11 **Systemic Neural Stem Cell-Based Therapeutic Interventions for**

Chapter 12 **Cell Adhesion Molecules in Neural Stem Cell and Stem Cell-Based Therapy for Neural Disorders 349**

Chapter 14 **Primary Neural Stem Cell Cultures from Adult Pig Brain and**

**Their Nerve-Regenerating Properties: Novel Strategies for**

During the last two decades stem cell biology has changed the field of basic research in life science as well as our perspective of its possible outcomes in medicine. At the beginning of the nineties, the discovery of neural stem cells in the mammalian central nervous system (CNS) made the generation of new neurons a real biological process occurring in the adult brain. Since then, a vast community of neuroscientists started to think in terms of regenerative medicine as a possible solution for incurable CNS diseases, such as traumatic injuries, stroke and neurode‐ generative disorders. Nevertheless, in spite of the remarkable expansion of the field, the devel‐ opment of techniques to image neurogenesis in vivo, sophisticated in vitro stem cell cultures, and experimental transplantation techniques, no efficacious therapies capable of restoring CNS structure and functions through cell replacement have been convincingly developed so far. Deep anatomical, developmental, molecular and functional investigations have shown that new neurons can be generated only within restricted brain regions under the control of specific environmental signals. In the rest of the CNS, many problems arise when stem cells encounter the mature parenchyma, which still behaves as 'dogmatically' static tissue. More recent studies have added an additional level of complexity, specifically in the context of CNS structural plas‐ ticity, where stem cells lie within germinal layer-derived neurogenic sites whereas progenitor cells are widespread through the CNS.

Hence, two decades after the seminal discovery of neural stem cells, the real astonishing fact is the occurrence of such cells in a largely nonrenewable tissue. Still, the most intriguing question is which possible functional or evolutionary reasons might justify such oddity.

In other self-renewing tissues, such as skin, cornea, and blood, the role of stem cells in the tis‐ sue homeostasis is largely known and efficacious stem cell therapies are already available. The most urgent question is whether and how the potential of neural stem cells could be exploited within the harsh territory of the mammalian CNS. In this case, unlike other tissues, more in‐ tense and time-consuming basic research is required before achieving a regenerative outcome. The road of such research should travel through a better knowledge of several aspects which are still poorly understood, including the developmental programs leading to postnatal brain maturation, the heterogeneity of progenitor cells involved, the bystander effect that stem cell grafts exert even in the absence of cell replacement, and the cohort of stem cell-to-tissue interac‐ tions occurring both in homeostatic and pathological conditions.

In this book, the experience and expertise of many leaders in neural stem cell research are gathered with the aim of making the point on a number of extremely promising, yet unresolved, issues.

> **Luca Bonfanti DVM, PhD** Dept. of Veterinary Sciences, University of Turin Neuroscience Institute Cavalieri-Ottolenghi (NICO)

**Section 1**

**Neural Stem Cells as Progenitor Cells**

**Neural Stem Cells as Progenitor Cells**

**Chapter 1**

**Systems for** *ex-vivo* **Isolation and**

Simona Casarosa, Jacopo Zasso and Luciano Conti

During neural development, a relatively small and formerly considered homogeneous population of Neural Stem cells (NSCs) gives rise to the extraordinary complexity proper of the Central Nervous System (CNS). These represent populations of self-renewing multipotent cells able to differentiate into a variety of neuronal and glial cell types in a time- and regionspecific manner throughout developmental stages and that account for a weak regenerative

In the adult mammalian CNS, the presence of NSCs has been extensively investigated in two regions, the SVZ and the SGZ of the hippocampus, two specialized niches that control NSCs divisions in order to physiologically regulate their proliferative (symmetrical divisions) *vs*

In the early '90s it was shown that NSCs could be extracted from the developing and adult

This has represented a key step in the field, since the obtainment of *in vitro* NSC sys‐ tems has been very useful in the last years in order to progress toward disclosure of the complex interplay of different extrinsic (signaling pathways) and intrinsic (transcription factors and epigenetics) signals that govern identity and functional properties of brain tissue-specific stem/progenitors [3]. Furthermore, it will also be a key step towards their exploitation for a better dissection of the molecular processes occurring in neurodegenera‐ tion [4]. Finally, NSC systems might represent major tools for the potential development of new cell-based and pharmacological treatments of neurodegenerative disorders and for

and reproduction in any medium, provided the original work is properly cited.

© 2013 Casarosa et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

mammalian brain and expanded/manipulated/differentiated *in vitro* (Fig. 1)*.*

**Culturing of Neural Stem Cells**

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/55137

potential in the adult brain [1].

differentiative fate (asymmetrical divisions) [2].

assaying their toxicological effects [5].

**1. Introduction**

#### **Chapter 1**
