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Title: The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration
The mechanism that causes the Alzheimer’s disease (AD) pathologies, including amyloid plaque, neurofibrillary tangles, and neuron death, is not well understood due to the lack of robust study models for human brain. Three-dimensional organoid systems based on human pluripotent stem cells (hPSCs) have shown a promising potential to model neurodegenerative diseases, including AD. These systems, in combination with engineering tools, allow in vitro generation of brain-like tissues that recapitulate complex cell-cell and cell-extracellular matrix (ECM) interactions. Brain ECMs play important roles in neural differentiation, proliferation, neuronal network, and AD progression. In this contribution related to brain ECMs, recent advances in modeling AD pathology and progression based on hPSC-derived neural cells, tissues, and brain organoids were reviewed and summarized. In addition, the roles of ECMs in neural differentiation of hPSCs and the influences of heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and hyaluronic acid on the progression of neurodegeneration were discussed. The advantages that use stem cell-based organoids to study neural degeneration and to investigate the effects of ECM development on the disease progression were highlighted. The contents of this article are significant for understanding cell-matrix interactions in stem cell microenvironment for treating neural degeneration.  more » « less
Award ID(s):
1652992
NSF-PAR ID:
10113234
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Cells
Volume:
8
Issue:
3
ISSN:
2073-4409
Page Range / eLocation ID:
242
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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    This article was corrected on 18 July 2022. See the end of the full text for details.

    Basic Protocol 1: Differentiation of hPSCs to neural crest

    Basic Protocol 2: Differentiation of neural crest to brain pericyte‐like cells

    Support Protocol 1: Flow cytometry analysis of neural crest cells

    Support Protocol 2: Maintenance, cryopreservation, and recovery of neural crest cells

    Support Protocol 3: Molecular characterization of brain pericyte‐like cells

    Support Protocol 4: Cord formation assay with endothelial cells and brain pericyte‐like cells

     
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