Human Induced Pluripotent stem cells and their derivatives for disease modeling and therapeutic applications in Alzheimer's disease

TY - CHAP

T1 - Human Induced Pluripotent stem cells and their derivatives for disease modeling and therapeutic applications in Alzheimer's disease

AU - Pires, C.

AU - Hall, V.

AU - Freude, K. K.

PY - 2016/5/20

Y1 - 2016/5/20

N2 - Human induced pluripotent stem cells (hiPSCs) have recently been generated for various inherited diseases. These hiPSC have the capacity to differentiate into any given cell type withthe help of small compounds and growth factors aiding the process. In Alzheimer’s disease (AD) several specific neural subpopulations in the brain are more susceptible to degeneration and apoptosis and hiPSCs can be used in order to generate these subpopulations in cell culture dishes via directed differentiation. Subsequently these cells can be used to optimize small compound screens to identify novel drug targets and to study AD pathology on a cellular level. Recently, it has also become possible to repair the genetic defect found in familiar forms of AD (FAD) through the application of CRISPR Cas9 mediated gene editing. Both hiPSC from FAD patients and isogenic controls generated via gene editing provide an excellent basis for investigation of cellular pathologies of AD and a screening platform to develop novel drugs for treatment. Furthermore, the current efforts to optimize neural 3D differentiation methods provide an even more natural platform compared to 2D differentiation approaches. These human cellular platforms complete, but also in some cases contradict the already gathered knowledge obtained from AD transgenic animals. This further underlines the importance of human based cellular models to fully understand AD pathology. In this chapter we will first summarize the current status of hiPSCfor AD, followed by a description of the methods used to generate isogenic controls. We will also discuss the possibilities and limitations of current neural differentiation protocols for AD to obtain relevant neuronal subtypes. In the end we will elaborate on the possibilities and current issues of hiPSC for cell replacement therapies in AD.

AB - Human induced pluripotent stem cells (hiPSCs) have recently been generated for various inherited diseases. These hiPSC have the capacity to differentiate into any given cell type withthe help of small compounds and growth factors aiding the process. In Alzheimer’s disease (AD) several specific neural subpopulations in the brain are more susceptible to degeneration and apoptosis and hiPSCs can be used in order to generate these subpopulations in cell culture dishes via directed differentiation. Subsequently these cells can be used to optimize small compound screens to identify novel drug targets and to study AD pathology on a cellular level. Recently, it has also become possible to repair the genetic defect found in familiar forms of AD (FAD) through the application of CRISPR Cas9 mediated gene editing. Both hiPSC from FAD patients and isogenic controls generated via gene editing provide an excellent basis for investigation of cellular pathologies of AD and a screening platform to develop novel drugs for treatment. Furthermore, the current efforts to optimize neural 3D differentiation methods provide an even more natural platform compared to 2D differentiation approaches. These human cellular platforms complete, but also in some cases contradict the already gathered knowledge obtained from AD transgenic animals. This further underlines the importance of human based cellular models to fully understand AD pathology. In this chapter we will first summarize the current status of hiPSCfor AD, followed by a description of the methods used to generate isogenic controls. We will also discuss the possibilities and limitations of current neural differentiation protocols for AD to obtain relevant neuronal subtypes. In the end we will elaborate on the possibilities and current issues of hiPSC for cell replacement therapies in AD.

M3 - Book chapter

SP - 1

EP - 25

BT - Alzheimer's disease

PB - SMGroup

ER -