Stem cells and neurodegenerative diseases (7)
Three-dimensional (3D) studies using stem cells: application in neurodegeneration and neurodegenerative diseases
Continuation. The beginning of the article is here.
In vitro stem cell studies are the best possible alternative to animal models, as they involve the use of cells of human origin and the data obtained can be easily extrapolated to humans. However, two-dimensional in vitro studies have many limitations. A two-dimensional culture is a homogeneous population of cells that does not reflect complex intercellular interactions. Such cultures do not reproduce the complex microenvironment and physiological parameters of organs. These limitations of research using two-dimensional cultures have made it possible to overcome three-dimensional cultures that have found wide application in the field of neuroscience. Such cultures have made it possible to achieve great achievements in reproducing the process of brain development; the literature also describes the successful production of three-dimensional brain organoids.
Alzheimer's disease has been very actively modeled using stem cells and two-dimensional cultures of neurons obtained from iPSCs, however, a serious limitation of this approach is the diffusion of beta-amyloid aggregates, which are gradually washed out of their environment with successive changes of the culture medium. Therefore, it was suggested that three-dimensional stem cell models of Alzheimer's disease would provide modeling of a more compact and full-fledged microenvironment of the brain, the local niche of which would provide the possibility of accumulating a sufficient number of beta-amyloid aggregates. Recently, this theory was confirmed in experiments in which ReN cells were cultured in three-dimensional matrigel systems to simulate familial Alzheimer's disease. The cells showed increased levels of phosphorylated tau protein, which is a confirmation of the higher efficiency of reproducing the pathophysiology of the disease on three-dimensional stem cell models. Zhang et al. the successful reproduction of reactions occurring in vivo in a three-dimensional cultural model of Alzheimer's disease was described. The study used a neuronal culture derived from neuroepithelial stem cells grown in a PuraMatrix hydrogel consisting of a self-assembling peptide matrix and laminin. The observations confirmed that the three-dimensional microenvironment provides recognition of beta-amyloid with the participation of p21-activated kinase. Protocols for the production of genetically modified human nerve progenitor cells have been standardized and published.
It has been repeatedly described in the literature that mouse iPSCs and embryonic stem cells demonstrate a higher potential for dopaminergic differentiation in a peptide three-dimensional nanofiber framework. The three-dimensional culture provides the best microenvironment for the formation of dopaminergic neurons demonstrating excitation with sufficient bioelectric potential and expressing specific markers. A successful differentiation of mesenchymal stem cells isolated from chorion into motor neurons in a three-dimensional nanofiber gelatin matrix has recently been described. These motor neurons should provide the possibility of three-dimensional modeling of amitrophic lateral sclerosis.
Figure 2. The most important studies/discoveries (five points each) concerning the main neurodegenerative diseases and prospects for the use of stem cells in their treatment, presented in a temporary order.
Ending: Final comments
Portal "Eternal youth" http://vechnayamolodost.ru
17.03.2017