Incomplete regeneration and restoration of function in damaged nerves is a major clinical challenge. In this regard, stem cells hold much promise in nerve tissue engineering, with advantages such as prevention of scar‐tissue ingrowth and guidance of axonal regrowth. Engineering 3D and patterned microenvironments using biomaterials with chemical and mechanical characteristics close to those of normal nervous tissue has enabled new approaches for guided differentiation of various stem cells toward neural cells and possible treatment of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Differentiation of stem cells in a neurogenic lineage is largely affected by signals from the surrounding microenvironment (niche). The stem cell niche refers to a specific microenvironment around the stem cells, which provides specific biochemical (soluble factors) and biophysical signals (topography, electrical, and mechanical). This specified niche regulates the stem cells' behavior and fate. While the role of chemical cues in neural differentiation is well appreciated, recently, the cues presented by the physical microenvironment are increasingly documented to be important regulators of nerve cell differentiation. The single and synergistic effects of surface topography and electrical signals on neural differentiation of stem cells are reviewed.
- Award ID(s):
- 2113403
- PAR ID:
- 10462012
- Date Published:
- Journal Name:
- Frontiers in Chemical Engineering
- Volume:
- 4
- ISSN:
- 2673-2718
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
The neural stem cell niche is a complex microenvironment that includes cellular factors, secreted factors, and physical factors that impact stem cell behavior and development. Cellular interactions through cadherins, cell–cell binding proteins, have implications in embryonic development and mesenchymal stem cell differentiation. However, little is known about the influence of cadherins within the neural stem cell microenvironment and their effect on human stem cell maintenance and differentiation. Therefore, the purpose of this study was to develop synthetic substrates to examine the effect of cadherin mechanotransduction on human neural stem cells. Glass substrates were fabricated using silane, protein A, and recombinant N-cadherin; we used these substrates to examine the effect of N-cadherin binding on neural stem cell proliferation, cytoskeletal structure and morphology, Yes-associated protein-1 (YAP) translocation, and differentiation. Bound exogenous N-cadherin induced concentration-dependent increases in adherens junction formation, YAP translocation, and early expression of neurogenic differentiation markers. Strong F-actin ring structures were initiated by homophilic N-cadherin binding, eliciting neuronal differentiation of cells within 96 h without added soluble differentiation factors. Our findings show that active N-cadherin binding plays an important role for differentiation of human iPS-derived neural stem cells towards neurons, providing a new tool to differentiate cells in vitro.more » « less
-
Decapod crustaceans, like mammals, retain the ability to make new neurons throughout life. In mammals, immune cells are closely associated with stem cells that generate adult-born neurons. In crayfish, evidence suggests that immune cells (hemocytes) originating in the immune system travel to neurogenic regions and transform into neural progenitor cells. This nontraditional immune activity takes place continuously under normal physiological conditions, but little is known under pathological conditions (neurodegeneration). In this study, the immune system and its relationship with neurogenesis were investigated during neurodegeneration (unilateral antennular ablation) in adult crayfish. Our experiments show that after ablation (1) Proliferating cells decrease in neurogenic areas of the adult crayfish brain; (2) The immune response, but not neurogenesis, is ablation-side dependent; (3) Inducible nitric oxide synthase (iNOS) plays a crucial role in the neurogenic niche containing neural progenitors during the immune response; (4) Brain areas targeted by antennular projections respond acutely (15 min) to the lesion, increasing the number of local immune cells; (5) Immune cells are recruited to the area surrounding the ipsilateral neurogenic niche; and (6) The vasculature in the niche responds acutely by dilation and possibly also neovascularization. We conclude that immune cells are important in both neurodegeneration and neurogenesis by contributing in physiological conditions to the maintenance of the number of neural precursor cells in the neurogenic niche (neurogenesis), and in pathological conditions (neurodegeneration) by coordinating NO release and vascular responses associated with the neurogenic niche. Our data suggest that neural damage and recovery participate in a balance between these competing immune cell roles.more » « less
-
more » « less
Abstract The vast majority of neural stem cell studies have been conducted on the brains of mice and rats, the classical model rodent. Non‐model organisms may, however, give us some important insights into how to increase neural stem cell numbers for regenerative purposes and with this in mind we have characterized these cells in the brain of the spiny mouse,
Acomys cahirinus . This unique mammal is highly regenerative and damaged tissue does not scar or fibrose. We find that there are more than three times as many stem cells in the SVZ and more than 3 times as many proliferating cells compared to the CD‐1 outbred strain of lab mouse. These additional cells create thick stem cell regions in the wall of the SVZ and very obvious columns of cells moving into the rostral migratory stream. In the dentate gyrus, there are more than 10 times as many cells proliferating in the sub‐granular layer and twice the number of doublecortin expressing neuroblasts. A preliminary analysis of some stem cell niche genes has identifiedSox2 ,Notch1 ,Shh , andNoggin as up‐regulated in the SVZ ofAcomys andBmp2 as being down‐regulated. The highly increased neural stem cell numbers inAcomys may endow this animal with increased regenerative properties in the brain or improved physiological performance important for its survival. -
more » « less
Abstract The mouse subventricular zone (SVZ) produces neurons throughout life. It is useful for mechanism discovery and is relevant for regeneration. However, the SVZ is deep, significantly restricting live imaging since current methods do not extend beyond a few hundred microns. We developed and adapted three-photon microscopy (3PM) for non-invasive deep brain imaging in live mice, but its utility in imaging the SVZ niche was unknown. Here, with fluorescent dyes and genetic labeling, we show successful 3PM imaging in the whole SVZ, extending to a maximum depth of 1.5 mm ventral to the dura mater. 3PM imaging distinguished multiple SVZ cell types in postnatal and juvenile mice. We also detected fine processes on neural stem cells interacting with the vasculature. Previous live imaging removed overlying cortical tissue or lowered lenses into the brain, which could cause inflammation and alter neurogenesis. We found that neither astrocytes nor microglia become activated in the SVZ, suggesting 3PM does not induce major damage in the niche. Thus, we show for the first time 3PM imaging of the SVZ in live mice. This strategy could be useful for intravital visualization of cell dynamics, molecular, and pathological perturbation and regenerative events.
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fceng.2022.1086099
