Soluble factors influencing the neural stem cell niche in brain physiology, inflammation, and aging

Willis, Cory M.; Nicaise, Alexandra M.; Krzak, Grzegorz; Ionescu, Rosana-Bristena; Pappa, Vasiliki; D'Angelo, Andrea; Agarwal, Ravi P.; Repollés-de-Dalmau, Maria; Peruzzotti-Jametti, ﻿Luca; Pluchino, ﻿Stefano

doi:10.1016/j.expneurol.2022.114124

Cited by 26 publications

(20 citation statements)

References 139 publications

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“…With the wide adoption of single-cell RNA sequencing and "omics" techniques, it was recently shown that both NPCs and OPCs express genes that are typically attributed to immune cells (Falcão et al, 2018;Kirby et al, 2019;Kirby and Castelo-Branco, 2020;Nicaise et al, 2020;Watson et al, 2020;Belenguer et al, 2021;Willis et al, 2022;Dittmann et al, 2023). For example, NPCs and OPCs express MHC (major histocompatibility complex) class I antigen presentation category genes (Falcão et al, 2018;Kirby et al, 2019;Lin et al, 2021;Dittmann et al, 2023).…”

Section: "Immune" Roles Of Npcs In Cns Development and Regenerationmentioning

confidence: 99%

Regulation of microglia function by neural stem cells

Almeida

Goodkey

Voronova

2023

Front. Cell. Neurosci.

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Neural stem and precursor cells (NPCs) build and regenerate the central nervous system (CNS) by maintaining their pool (self-renewal) and differentiating into neurons, astrocytes, and oligodendrocytes (multipotency) throughout life. This has inspired research into pro-regenerative therapies that utilize transplantation of exogenous NPCs or recruitment of endogenous adult NPCs for CNS regeneration and repair. Recent advances in single-cell RNA sequencing and other “omics” have revealed that NPCs express not just traditional progenitor-related genes, but also genes involved in immune function. Here, we review how NPCs exert immunomodulatory function by regulating the biology of microglia, immune cells that are present in NPC niches and throughout the CNS. We discuss the role of transplanted and endogenous NPCs in regulating microglia fates, such as survival, proliferation, migration, phagocytosis and activation, in the developing, injured and degenerating CNS. We also provide a literature review on NPC-specific mediators that are responsible for modulating microglia biology. Our review highlights the immunomodulatory properties of NPCs and the significance of these findings in the context of designing pro-regenerative therapies for degenerating and diseased CNS.

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Section: "Immune" Roles Of Npcs In Cns Development and Regenerationmentioning

confidence: 99%

Regulation of microglia function by neural stem cells

Almeida

Goodkey

Voronova

2023

Front. Cell. Neurosci.

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“…While cells with the characteristics of “stem or progenitor” cells can be isolated from the adult brain of many species, their density and function declines with age [ 76 , 77 ], a time in life that many people would need them for regeneration of brain elements that are damaged by disease. Certainly, such cells may be “primed” to contribute to neural regeneration as being in a specific location can lead to adaptations (i.e., lectin phenotypes, epigenetic signatures; discussed in [ 26 ]) and thus may be destined to serve specific roles in the brain.…”

Section: Limitations Regarding Use Of Brain-associated Nscmentioning

confidence: 99%

Use of Brain-Derived Stem/Progenitor Cells and Derived Extracellular Vesicles to Repair Damaged Neural Tissues: Lessons Learned from Connective Tissue Repair Regarding Variables Limiting Progress and Approaches to Overcome Limitations

Hart

2023

IJMS

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Pluripotent neural stem or progenitor cells (NSC/NPC) have been reported in the brains of adult preclinical models for decades, as have mesenchymal stem/stromal cells (MSC) been reported in a variety of tissues from adults. Based on their in vitro capabilities, these cell types have been used extensively in attempts to repair/regenerate brain and connective tissues, respectively. In addition, MSC have also been used in attempts to repair compromised brain centres. However, success in treating chronic neural degenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and others with NSC/NPC has been limited, as have the use of MSC in the treatment of chronic osteoarthritis, a condition affecting millions of individuals. However, connective tissues are likely less complex than neural tissues regarding cell organization and regulatory integration, but some insights have been gleaned from the studies regarding connective tissue healing with MSC that may inform studies attempting to initiate repair and regeneration of neural tissues compromised acutely or chronically by trauma or disease. This review will discuss the similarities and differences in the applications of NSC/NPC and MSC, where some lessons have been learned, and potential approaches that could be used going forward to enhance progress in the application of cellular therapy to facilitate repair and regeneration of complex structures in the brain. In particular, variables that may need to be controlled to enhance success are discussed, as are different approaches such as the use of extracellular vesicles from stem/progenitor cells that could be used to stimulate endogenous cells to repair the tissues rather than consider cell replacement as the primary option. Caveats to all these efforts relate to whether cellular repair initiatives will have long-term success if the initiators for neural diseases are not controlled, and whether such cellular initiatives will have long-term success in a subset of patients if the neural diseases are heterogeneous and have multiple etiologies.

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“…Conversely, the downregulated GPR19 data cohorts were more strongly associated with ‘Interleukin signaling’, ‘mTOR signaling’, ‘IGF-1 signaling’ and ‘Nuclear Laminopathies’. All of these diverse functions strongly converge with respect to the pathomechanisms linked to pathological aging (DNA damage—[ 73 ]; Cholesterol regulation [ 188 , 189 , 190 ]; stem cell management [ 191 , 192 ]; UPR [ 193 , 194 ]; mTOR signaling [ 195 , 196 ]; IGF-1 signaling [ 197 , 198 ]; laminopathies [ 199 , 200 ]).…”

Section: Functional Gpr19 Molecular Signaturesmentioning

confidence: 99%

Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process

Maudsley

Walter

Schrauwen

et al. 2022

IJMS

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G protein-coupled receptors (GPCRs) represent one of the most functionally diverse classes of transmembrane proteins. GPCRs and their associated signaling systems have been linked to nearly every physiological process. They also constitute nearly 40% of the current pharmacopeia as direct targets of remedial therapies. Hence, their place as a functional nexus in the interface between physiological and pathophysiological processes suggests that GPCRs may play a central role in the generation of nearly all types of human disease. Perhaps one mechanism through which GPCRs can mediate this pivotal function is through the control of the molecular aging process. It is now appreciated that, indeed, many human disorders/diseases are induced by GPCR signaling processes linked to pathological aging. Here we discuss one such novel member of the GPCR family, GPR19, that may represent an important new target for novel remedial strategies for the aging process. The molecular signaling pathways (metabolic control, circadian rhythm regulation and stress responsiveness) associated with this recently characterized receptor suggest an important role in aging-related disease etiology.

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Soluble factors influencing the neural stem cell niche in brain physiology, inflammation, and aging

Cited by 26 publications

References 139 publications

Regulation of microglia function by neural stem cells

Regulation of microglia function by neural stem cells

Use of Brain-Derived Stem/Progenitor Cells and Derived Extracellular Vesicles to Repair Damaged Neural Tissues: Lessons Learned from Connective Tissue Repair Regarding Variables Limiting Progress and Approaches to Overcome Limitations

Intersection of the Orphan G Protein-Coupled Receptor, GPR19, with the Aging Process

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