Neural+Stem+Cells

Group Members: Maryam Nazir, Asuka Sihui Guan, Ji Wu, Dai Hyun

Neural stem cells are a population of self-renewing, multipotent cells within the central nervous system (1). The discovery of neural stem cells (NSCs), and subsequent research, has led to widespread excitement over the possibility of transforming medicine through regeneration (2). NSCs have indeed been successfully reintroduced into the central nervous system after isolation, proliferation, and manipulation in vitro (3). In addition to the medical prospects, stem cells have been a useful tool in comprehending basic biological processes such as development, repair, and cancer (1). NSCs produce the immense diversity of neurons, oligodendrocytes, and astrocytes in the developing central nervous system and they have an important role in animals with regards to learning and plasticity in adulthood. Although surrounded by controversy, the use of NSCs in treating stroke, tumours, and neurodegenerative disease, such as Parkinson’s disease, is of particular interest to many researchers around the world today (2). Since their discovery, the roles of NSCs during embryonic development and in adult neurogenesis have been elucidated, as well as their mechanisms of differentiation and proliferation. Currently, research is focused on approaches such as the use of NSCs in disease models and drugs screens and the strategy of using NSCs in gene therapy for the treatment of neurological disease.

1. Adult neural stem cell in neurogenesis (Sihui Guan) > 1.1 Overview > 1.2 NSCs in Adult Mammalian brains >> 1.2.1 SGZ in Hippocampal Dentate Gyrus >> 1.2.2 SVZ in the Lateral Ventricle > 1.3 Adult Neurogenesis Pathways >> 1.3.1 Adult Neurogenesis in Hippocampus >> 1.3.2 Adult Neurogenesis in Olfactory Bulb >> 1.3.3 Adult NSCs Activation > 1.4 Functions of Adult Neurogenesis >> 1.4.1 Roles in hippocampal-dependent activities >>> 1.4.1.1 Hippocampal Synaptic Plasticity and Circuitry Modulation >>> 1.4.1.2 Effect on Learning and Memory >>> 1.4.1.3 Mood Regulation >> 1.4.2 Roles in odorant-dependent learning >> 1.4.3 Potential roles in CNS injury repair

**2. Mechanisms of Differentiation and Proliferation (**//Dai Hyun//**)**

a. Overviews of the different types of cellular components that are responsible for the neuronal cell differentiation and proliferation. b. Regulation of neurogenesis by hormones. c. Regulation of neurogenesis by growth factors.

3. Neural Stem Cell Gene Therapy (//Maryam Nazir//)

> 3.1 Tropism towards brain pathology >> 3.1.1 Pathotropic factors >> 3.1.2 Receptors >> 3.1.3 Physiological processes shaping migration > 3.2 Neural stem cells as delivery vehicles >> 3.2.1 Primary cells >> 3.2.2 Immortalization >> 3.2.3 Embryonic stem cells and embryonic stem cell-derived cells > 3.3 Genetic manipulation >> 3.3.1 Viral vectors > 3.4 Suitable disease targets and therapeutic strategies >> 3.4.1 Alzheimer's disease >> 3.4.2 Parkinson's disease >> 3.4.3 Disorders of brain metabolism >> 3.4.4 Brain malignancy >>> 3.4.4a Molecular and immunologic strategies

**4.** Disease Model, Drug Screen and Transplantation Trials ( // __Ji Wu__ // )

> 4.1 Disease models as a tool to study disease pathology > 4.2 Interaction between susceptible genes and environmental factors >> 4.2a Epigenetic modification >> 4.2b Circuit connections and complex brain environment > 4.3 Drug screen > 4.4 Stem cell based therapy >> 4.4a Transplantation Trials in Parkinson's Disease >> 4.4b Astrocyte replacement in ALS

**References:**

1. Gage, F. H. Mammalian neural stem cells. //Science// **287**, 1433–143 (2000). 2. Kochar, P. G. What are stem cells? Dec 2004 [cited 2012 Jan 5]. Available from: http://www.csa.com/discoveryguides/stemcell/overview.php 3. Bithell, A., Williams, B. P. Neural stem cells and cell replacement therapy: making the right cells. //Clinical Science// **108**, 13–22 (2005).

Neural stem cells are a population of self-renewing, multipotent cells within the central nervous system1. The discovery of neural stem cells (NSCs), and subsequent research, has led to widespread excitement over the possibility of transforming medicine through regeneration2. NSCs have indeed been successfully reintroduced into the central nervous system after isolation, proliferation, and manipulation in vitro3. In addition to the medical prospects, stem cells have been a useful tool in comprehending basic biological processes such as development, repair, and cancer1. NSCs produce the immense diversity of neurons, oligodendrocytes, and astrocytes in the developing central nervous system and they have an important role in animals with regards to learning and plasticity in adulthood. Although surrounded by controversy, the use of NSCs in treating stroke, tumours, and neurodegenerative disease, such as Parkinson’s disease, is of particular interest to many researchers around the world today2. Since their discovery, the roles of NSCs during embryonic development and in adult neurogenesis have been elucidated, as well as their mechanisms of differentiation and proliferation. Currently, research is focused on approaches such as the use of NSCs in disease models and drugs screens and the strategy of using NSCs in gene therapy for the treatment of neurological disease. **1. Embryonic and Adult neural stem cell in neurogenesis (Sihui Guan )** a. Overviews of embryonic and adults neural stem cells: types, locations and basic functions b. The neural cell lineage in embryonic development c. Roles of adult neural stem cells in neuroregenesis **2. Mechanisms of Differentiation and Proliferation (Dai Hyun)** a. Overviews of the different types of cellular components that are responsible for the neuronal cell differentiation and proliferation. b. Regulation of neurogenesis by hormones. c. Regulation of neurogenesis by growth factors. **3. Gene Therapy (Maryam Nazir)** a. Tropism towards brain pathology b. Neural stem cell delivery vehicles and their genetic manipulation c. Delivery of therapeutic substances and experimental outcomes d. Suitable disease targets **4. Disease Model and Drug Screen (Ji Wu)**| a. Disease models as a tool to identify disease susceptible genes <span style="display: block; font-family: 'Times New Roman',Times,serif; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">b. Interaction between susceptible genes and environmental factors <span style="display: block; font-family: 'Times New Roman',Times,serif; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">c. Application of stem cell model for drug discovery as predictors of new and improved drug treatments <span style="display: block; font-family: 'Times New Roman',Times,serif; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">**References:** <span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 10pt; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">1. Gage, F. H. Mammalian neural stem cells. //Science// **287**, 1433–143 (2000). <span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 10pt; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">2. Kochar, P. G. What are stem cells? Dec 2004 [cited 2012 Jan 5]. Available from: <span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 10pt; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">http://www.csa.com/discoveryguides/stemcell/overview.php <span style="display: block; font-family: 'Times New Roman',Times,serif; font-size: 10pt; height: 1px; left: -40px; margin-bottom: 0cm; overflow-x: hidden; overflow-y: hidden; position: absolute; text-indent: 36pt; top: -25px; width: 1px;">3. Bithell, A., Williams, B. P. Neural stem cells and cell replacement therapy: making the right cells. //Clinical Science// **108**, 13–22 (2005).

<span style="display: block; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3. Neural stem cell gene therapy (// Maryam Nazir //) <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.1 Tropism towards brain pathology <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.1.1 Pathotropic factors <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.1.2 Receptors <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.1.3 Physiological processes shaping migration <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.1.3a Inflammation <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.1.3b Reactive astrocytosis <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.2 Neural stem cells as delivery vehicles <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.2.1 Primary cells <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.2.2 Immortalization <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.2.3 Human embryonic stem cell-derived cells <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.3 Genetic manipulation <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.3.1 Viral vectors <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.4 Suitable disease targets and therapeutic strategies <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.4.1 Alzheimer’s disease <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.4.2 Parkinson’s disease <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.4.3 Disorders of brain metabolism <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.4.4 Brain malignancy <span style="display: block; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 406px; width: 1px;">3.4.4a Molecular and immunologic strategies

<span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3. Neural stem cell gene therapy (// Maryam Nazir //) <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.1 Tropism towards brain pathology <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.1.1 Pathotropic factors <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.1.2 Receptors <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.1.3 Physiological processes shaping migration <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.2 Neural stem cells as delivery vehicles <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.2.1 Primary cells <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.2.2 Immortalization <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.2.3 Human embryonic stem cell-derived cells <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.3 Genetic manipulation <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.3.1 Viral vectors <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.4 Suitable disease targets and therapeutic strategies <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.4.1 Alzheimer’s disease <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.4.2 Parkinson’s disease <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.4.3 Disorders of brain metabolism <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.4.4 Brain malignancy <span style="display: block; font-size: 12pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 628px; width: 1px;">3.4.4a Molecular and immunologic strategies

<span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3. Neural stem cell gene therapy (// Maryam Nazir //) <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.1 Tropism towards brain pathology <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.1.1 Pathotropic factors <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.1.2 Receptors <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.1.3 Physiological processes shaping migration <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.2 Neural stem cells as delivery vehicles <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.2.1 Primary cells <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.2.2 Immortalization <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.2.3 Human embryonic stem cell-derived cells <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.3 Genetic manipulation <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.3.1 Viral vectors <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.4 Suitable disease targets and therapeutic strategies <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.4.1 Alzheimer’s disease <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.4.2 Parkinson’s disease <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.4.3 Disorders of brain metabolism <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.4.4 Brain malignancy <span style="display: block; font-size: 10pt; height: 1px; left: -40px; line-height: normal; overflow-x: hidden; overflow-y: hidden; position: absolute; top: 1583px; width: 1px;">3.4.4a Molecular and immunologic strategies