Human-derived neural progenitors functionally replace astrocytes in adult mice

Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su‐Chun

doi:10.1172/jci69097

Cited by 67 publications

(84 citation statements)

References 46 publications

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“…Number 9 September 2017 surrounded blood vessels (Supplemental Figure 9B), suggesting the formation of a blood-brain barrier (44). Ectopic cell collections were rare.…”

Section: Resultsmentioning

confidence: 99%

“…However, adverse effects of this glial outgrowth were not evident as either tumor formation or deterioration in forelimb function over time. Previously, Goldman and colleagues reported long-term safety and efficacy after administration of human glial progenitor cells in rodent demyelinating disease models (15), and Zhang and colleagues reported the functional integration of human-derived astrocytes into intact rodent spinal cord, including investment of astrocytic processes around host neurons and extension of end feet around blood vessels (44). Similarly, ectopic clusters of cells that have been previously reported (45,46) with our grafting technique were only rarely observed at prolonged time points (2 of 12 animals surviving 6 months or longer) and did not compress jci.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

Ceto²,

Wang³

et al. 2017

Journal of Clinical Investigation

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“…Number 9 September 2017 surrounded blood vessels (Supplemental Figure 9B), suggesting the formation of a blood-brain barrier (44). Ectopic cell collections were rare.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prolonged human neural stem cell maturation supports recovery in injured rodent CNS

Ceto²,

Wang³

et al. 2017

Journal of Clinical Investigation

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“…In vivo , transplantation of hSOD1 G93A glial-restricted precursor cells (lineage-restricted glial progenitors) into the spinal cord of wild-type animals induces motor neuron death and motor deficits [79]. A similar result was obtained when astrocytes differentiated from ALS patient-derived iPSCs where used for the transplant [80]. Moreover, chronic infusion of conditioned media from hSOD1 G93A -astrocyte cultures induces motor neuron degeneration and neuromuscular dysfunction in wild-type rats [81].…”

Section: Astrocyte-mediated Motor Neuron Toxicitymentioning

confidence: 95%

Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis

Pehar

Harlan

Killoy

et al. 2018

CPD

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Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function and survival in an injury-specific manner. In ALS patients, reactive astrocytes surround both upper and lower degenerating motor neurons and play a key role in the pathology. It has become clear that astrocytes play a major role in ALS pathology. Through loss of normal function or acquired new characteristics, astrocytes are able to influence motor neuron fate and the progression of the disease. The use of different cell culture models indicates that ALS-astrocytes are able to induce motor neuron death by secreting a soluble factor(s). Here, we discuss several pathogenic mechanisms that have been proposed to explain astrocyte-mediated motor neuron death in ALS. In addition, examples of strategies that revert astrocyte-mediated motor neuron toxicity are reviewed to illustrate the therapeutic potential of astrocytes in ALS. Due to the central role played by astrocytes in ALS pathology, therapies aimed at modulating astrocyte biology may contribute to the development of integral therapeutic approaches to halt ALS progression.

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“…These beneficial effects are believed to be linked to multiple mechanisms, including production of neurotrophic factors and reduction of microgliosis and macrogliosis, thus leading to increased resistance to death of motor neurons and neurodegeneration. In a series of longterm studies, Chen et al showed iPSC-derived neural progenitors mostly differentiated into astrocytes, replaced the endogenous astrocytes, formed networks through their processes, and encircled endogenous neurons [68]. Preclinical studies, currently being conducted at Johns Hopkins University, use human iPSC-derived glial-restricted precursors (iPSC-GRPs) [88] and may offer perspectives for the use of iPSC-based therapy in ALS [87].…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%