A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity_suppl2

Background:Neurodegenerative diseases like Alzheimer’s Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments.Summary:With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth. It is envisioned that iPSCs could be used as a powerful tool for neurodegenerative disease modelling and eventually be an unlimited source for cell replacement therapy. This paper provides an overview of; the contribution of iPSCs towards modeling and understanding AD pathogenesis, the novel human/mouse chimeric models in elucidating current AD pathogenesis hypotheses, the possible use of iPSCs in drug screening, and perspectives on possible future directions.Key messages:Human/mouse chimeric models using iPSCs to study AD offer much promise in better replicating AD pathology and can be further exploited to elucidate disease pathogenesis with regards to the neuroinflammation hypothesis of AD.

Download Full-text

Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells

Acta Pharmacologica Sinica ◽

10.1038/aps.2013.63 ◽

2013 ◽

Vol 34 (6) ◽

pp. 755-764 ◽

Cited By ~ 38

Author(s):

Xiao-hong Xu ◽

Zhong Zhong

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Drug Screening ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Neurological Diseases ◽

Induced Pluripotent

Download Full-text

The application of patient-derived induced pluripotent stem cells for modeling and treatment of Alzheimer’s disease

Brain Science Advances ◽

10.1177/2096595819896178 ◽

2019 ◽

Vol 5 (1) ◽

pp. 21-40 ◽

Cited By ~ 3

Author(s):

Fabin Han ◽

Chuanguo Liu ◽

Jin Huang ◽

Juanli Chen ◽

Chuanfei Wei ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Stem Cells ◽

Human Brain ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Disease Modeling ◽

Autologous Transplantation ◽

Human Ipscs ◽

Induced Pluripotent

Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disease which is mainly caused by aggregated protein plaques in degenerating neurons of the brain. These aggregated protein plaques are mainly consisting of amyloid β (Aβ) fibrils and neurofibrillary tangles (NFTs) of phosphorylated tau protein. Even though the transgenic murine models can recapitulate some of the AD phenotypes, they are not the human cell models of AD. Recent breakthrough in somatic cell reprogramming made it available to use induced pluripotent stem cells (iPSCs) for patientspecific disease modeling and autologous transplantation therapy. Human iPSCs provide alternative ways to obtain specific human brain cells of AD patients to study the molecular mechanisms and therapeutic approaches for familial and sporadic forms of AD. After differentiation into neuronal cells, iPSCs have enabled the investigation of the complex aetiology and timescale over which AD develops in human brain. Here, we first go over the pathological process of and transgenic models of AD. Then we discuss the application of iPSC for disease model and cell transplantation. At last the challenges and future applications of iPSCs for AD will be summarized to propose cell-based approaches for the treatment of this devastating disorder.

Download Full-text

Induced Pluripotent Stem Cells to Model and Treat Neurogenetic Disorders

Neural Plasticity ◽

10.1155/2012/346053 ◽

2012 ◽

Vol 2012 ◽

pp. 1-15 ◽

Cited By ~ 7

Author(s):

Hansen Wang ◽

Laurie C. Doering

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Neurological Diseases ◽

Cellular Reprogramming ◽

Cell Populations ◽

Therapeutic Implications ◽

Skin Biopsies ◽

Neurogenetic Disorders ◽

Induced Pluripotent

Remarkable advances in cellular reprogramming have made it possible to generate pluripotent stem cells from somatic cells, such as fibroblasts obtained from human skin biopsies. As a result, human diseases can now be investigated in relevant cell populations derived from induced pluripotent stem cells (iPSCs) of patients. The rapid growth of iPSC technology has turned these cells into multipurpose basic and clinical research tools. In this paper, we highlight the roles of iPSC technology that are helping us to understand and potentially treat neurological diseases. Recent studies using iPSCs to model various neurogenetic disorders are summarized, and we discuss the therapeutic implications of iPSCs, including drug screening and cell therapy for neurogenetic disorders. Although iPSCs have been used in animal models with promising results to treat neurogenetic disorders, there are still many issues associated with reprogramming that must be addressed before iPSC technology can be fully exploited with translation to the clinic.

Download Full-text