**Meet the editor**

Luca Bonfanti, DVM, PhD, graduated (with honors) in 1987 at the School of Veterinary Medicine of the University of Turin, Italy. After a PhD in Functional Neuroanatomy and a postdoc at the Bordeaux University, he was appointed Assistant Professor in 1994 and Associate Professor in 2000 at the Turin University. He is now Professor of Veterinary Anatomy at the Department

of Veterinary Sciences, and group leader at the Neuroscience Institute Cavalieri-Ottolenghi (NICO), a research center on brain repair. Since 1992 his research activity is devoted to study brain structural plasticity with particular reference to adult neurogenesis. In 2011 he was Visiting Professor at Northeastern University (Boston); he is receiving editor in the peer reviewed journal Frontiers in Neurogenesis.

Contents

**Preface VII**

**Stem Cells 3**

Verdon Taylor

Emília Madarász

**Section 1 Neural Stem Cells as Progenitor Cells 1**

Chapter 2 **Neural Stem Cell Heterogeneity 29**

Subramanian Dharmarajan

**Section 2 Neural Stem Cells and Neurogenesis 135**

Chapter 1 **Systems for ex-vivo Isolation and Culturing of Neural**

Simona Casarosa, Jacopo Zasso and Luciano Conti

Chapter 3 **Diversity of Neural Stem/Progenitor Populations: Varieties by Age, Regional Origin and Environment 45**

Teri L. Belecky-Adams, Ellen C. Chernoff, Jonathan M. Wilson and

Chapter 4 **Reactive Muller Glia as Potential Retinal Progenitors 73**

Chapter 6 **Postnatal Neurogenesis in the Subventricular Zone: A**

Manavendra Pathania and Angelique Bordey

Chapter 7 **Modulation of Adult Neurogenesis by the Nitric**

**Oxide System 163**

Araújo

**Manipulable Source for CNS Plasticity and Repair 137**

Bruno P. Carreira, Ana I. Santos, Caetana M. Carvalho and Inês M.

Chapter 5 **Neural Stem Cell: Tools to Unravel Pathogenetic Mechanisms and to Test Novel Drugs for CNS Diseases 119** Luca Colucci-D'Amato and MariaTeresa Gentile

## Contents

#### **Preface XI**



Preface

cells are widespread through the CNS.

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

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

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‐

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)

is which possible functional or evolutionary reasons might justify such oddity.

tions occurring both in homeostatic and pathological conditions.

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

Chapter 10 **A Survey of the Molecular Basis for the Generation of Functional Dopaminergic Neurons from Pluripotent Stem Cells: Insights from Regenerative Biology and Regenerative Medicine 271** Kaneyasu Nishimura, Yoshihisa Kitamura, Kiyokazu Agata and Jun Takahashi

