Utilising Induced Pluripotent Stem Cells in Neurodegenerative Disease Research: Focus on Glia

Abstract

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.

Cell Therapy for Neurological Disorders: The Perspective of Promising Cells

“…Therefore, transplantation of hOPCs may be a potential therapy for demyelinating diseases. On the other hand, astrocytes are the most numerous cell type in the brain, playing various functions, including maintaining homeostasis, providing neurotrophic support, and connecting neurons with the bloodstream [ 100 ]. The loss or dysfunction of astrocytes is related to many neurological disorders, such as stroke, epilepsy, and MS [ 101 ].…”

Therapeutic Potential of Astrocyte Transplantation

“…Replacement of damaged cells, including astrocyte-lineage cells, after spinal cord injury (SCI), has been discussed, alongside the use of biomaterials to aid in cell guidance and integration into the host tissues 55,56 . Several reviews focused on the regenerative potential of stem cells and progenitors such as glial-restricted precursor cells (GRPs) capable of differentiating into astrocytes among other cell types as sources of cellular grafts [57][58][59][60][61][62][63][64] , or the ability of transplanted stem cells to interact with the host astrocytes and stimulate protective pathways in the latter [65][66][67][68] in several conditions, including stroke, SCI, and Alzheimer's disease (AD). In particular, protection of the blood-brain barrier (BBB) and the neurovascular unit by transplanted astrocytes has received attention in studies of neurodegenerative diseases 63 .…”

Application of Small Molecules in the Central Nervous System Direct Neuronal Reprogramming

“…The main reason for this is the extremely limited neuron-regenerative capacity in the adult mammalian Central Nervous System (CNS), which contributes to the poor prognosis of patients with CNS injuries ( Goldman, 2016 ; Tedeschi et al, 2016 ; McMurran et al, 2018 ; Vignoles et al, 2019 ; Stricker and Gotz, 2021 ). In the last decades, stem cell transplantation therapy has been proposed to be an efficient method of replacing lost neurons in several neurological disorders ( Albert et al, 2021 ; Lu et al, 2021 ; Salikhova et al, 2021 ). However, some existing problems, such as teratogenic effect, differentiation abnormality, ethical issues, and survival limitation, prevent its clinical appilications ( Barker and de Beaufort, 2013 ; Qin et al, 2017 ; Zeng et al, 2021 ).…”