Advances and Current Challenges Associated with the Use of Human Induced Pluripotent Stem Cells in Modeling Neurodegenerative Disease

Abstract

One of the most profound advances in the last decade of biomedical research has been the development of human induced pluripotent stem cell (hiPSC) models for identification of disease mechanisms and drug discovery. Human iPSC technology has the capacity to revolutionize healthcare and the realization of personalized medicine, but differentiated tissues derived from stem cells come with major criticisms compared to native tissue, including variability in genetic backgrounds, a lack of functional maturity, and differences in epigenetic profiles. It is widely believed that increasing complexity will lead to improved clinical relevance, so methods are being developed that go from a single cell type to various levels of 2-D coculturing and 3-D organoids. As this inevitable trend continues, it will be essential to thoroughly understand the strengths and weaknesses of more complex models and to develop criteria for assessing biological relevance. We believe the payoff of robust, high-throughput, clinically meaningful human stem cell models could be the elimination of often inadequate animal models. To facilitate this transition, we will look at the challenges and strategies of complex model development through the lens of neurodegeneration to encapsulate where the disease-in-a-dish field currently is and where it needs to go to improve.

Harnessing Immunoproteostasis to Treat Neurodegenerative Disorders

“…However, it is difficult to envision how one can recreate all of the complex interactions between various cells in the brain, the blood-brain barrier, the circulatory system, the peripheral immune system, and environmental factors from iPSCs in a dish. Nevertheless, there is exciting work in this area, and valuable insights may emerge from such studies in the future (Berry et al, 2018).…”

Optimized culture of retinal ganglion cells and amacrine cells from adult mice

“…Neurons derived from neonates and iPSCs are easily generated in large quantities and can be cultured with excellent viability with extensive neurite outgrowth [3,6]. However, prior to isolation, these neurons are limited to genetic manipulation as well by their neuronal immaturity and epigenetic gap [56].…”

Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology

“…VEGFA is a proangiogenic factor, which also involves in neuroprotection, neurogenesis, synaptic plasticity, and modulation of inflammation and astrocyte proliferation (Harris et al, 2018;Wei et al, 2018). Recently, human induced pluripotent stem cells, which are produced from somatic cells by overexpressing four reprogramming factors (including MYC), were applying in the cellular therapy of NDs (Berry et al, 2018). ALB is the most plentiful protein in blood plasma and cerebrospinal fluid, where it contributes substantially to regulate the osmotic pressure and metabolic processes (Ts et al, 2017).…”