scholarly journals Immune-tolerance to human iPS-derived neural progenitors xenografted into the immature cerebellum is overridden by species-specific differences in differentiation timing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giulia Nato ◽  
Alessandro Corti ◽  
Elena Parmigiani ◽  
Elena Jachetti ◽  
Daniele Lecis ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Prenatal Development ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Neural Precursors ◽  
Adult Rat ◽  
Induced Pluripotent ◽  
Species Specific

AbstractWe xeno-transplanted human neural precursor cells derived from induced pluripotent stem cells into the cerebellum and brainstem of mice and rats during prenatal development or the first postnatal week. The transplants survived and started to differentiate up to 1 month after birth when they were rejected by both species. Extended survival and differentiation of the same cells were obtained only when they were transplanted in NOD-SCID mice. Transplants of human neural precursor cells mixed with the same cells after partial in vitro differentiation or with a cellular extract obtained from adult rat cerebellum increased survival of the xeno-graft beyond one month. These findings are consistent with the hypothesis that the slower pace of differentiation of human neural precursors compared to that of rodents restricts induction of immune-tolerance to human antigens expressed before completion of maturation of the immune system. With further maturation the transplanted neural precursors expressed more mature antigens before the graft were rejected. Supplementation of the immature cells suspensions with more mature antigens may help to induce immune-tolerance for those antigens expressed only later by the engrafted cells.

scholarly journals HIV antiretrovirals have differential effects on viability and function in human iPSC-derived neurons and neural precursor cells

2020 ◽  
Author(s):  
Alyson S. Smith ◽  
Soneela Ankam ◽  
Chen Farhy ◽  
Ranor C.B. Basa ◽  
Kara L. Gordon ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Model Systems ◽  
Neural Precursor ◽  
Hiv Replication ◽  
Induced Pluripotent ◽  
Developing Neurons ◽  
And Function

AbstractCombination antiretroviral therapy (cART) improves life expectancy and lowers the incidence of central nervous system (CNS) opportunistic infections, lymphomas, and HIV-associated dementia in HIV+ people. However, mild-to-moderate HIV-associated neurocognitive disorders (HAND) persist in about 50% of HIV+ people, even when HIV replication is well controlled. In vitro, animal model, and clinical studies suggest that cART neurotoxicity could be a contributing factor to the progression of HAND. In this study, we developed two in vitro model systems using glutamatergic neurons derived from human induced pluripotent stem cells (hiPSC-Gluts) and fetal neural precursor cells (hNPCs) to assay for antiretroviral (ARV) effects on mature and developing neurons, respectively. We tested four ARVs: the nucleoside/nucleotide reverse transcriptase inhibitors tenofovir disproxil fumarate (TDF) and emtricitabine (FTC) and the integrase inhibitors dolutegravir (DTG) and elvitegravir (EVG). DTG, EVG, and TDF decreased hiPSC-Glut viability and neurite length; all four antiretrovirals decreased hiPSC-Glut synapse counts; and DTG and EVG decreased the frequency and magnitude of hiPSC-Glut calcium transients. The magnitude of these neurotoxic effects increased with longer ARV exposure times and with the exposure of hiPSC-Gluts to two or three ARVs simultaneously. These results suggest that certain ARVs could cause HAND by decreasing the survival and function of CNS neurons. In fetal hNPCs, TDF decreased viability and changed the distribution of epigenetic histone modifications, suggesting that this ARV may alter neurogenesis, which could impair cognition in adults and/or CNS development for those exposed to ARV in utero or early childhood. Our study establishes human preclinical neurotoxicity systems that can screen for potential ARV CNS toxicity and develop safer cART regimens.

In vitro differentiation of E-N-CAM expressing rat neural precursor cells isolated by FACS during prenatal development

1994 ◽  
Vol 37 (3) ◽  
pp. 359-373 ◽  
Author(s):  
S. Blass-Kampmann ◽  
S. Reinhardt-Maelicke ◽  
A. Kindler-Röhrborn ◽  
V. Cleeves ◽  
M. F. Rajewsky
Keyword(s):  
Prenatal Development ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
In Vitro Differentiation

In vitro differentiation of human bone marrow stromal cells into neural precursor cells using small molecules

2021 ◽  
Vol 363 ◽  
pp. 109340
Author(s):  
Abeer Sallam ◽  
Thangirala Sudha ◽  
Noureldien H.E. Darwish ◽  
Samar Eghotny ◽  
Abeer E-Dief ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Small Molecules ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Precursor Cells ◽  
Marrow Stromal Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
In Vitro Differentiation

Adult human spinal cord harbors neural precursor cells that generate neurons and glial cells in vitro

2008 ◽  
Vol 86 (9) ◽  
pp. 1916-1926 ◽  
Author(s):  
C. Dromard ◽  
H. Guillon ◽  
V. Rigau ◽  
C. Ripoll ◽  
J.C. Sabourin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Glial Cells ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Human Spinal Cord ◽  
Adult Human

Comparison of the therapeutic potential of adult and embryonic neural precursor cells in a rat model of Parkinson disease

2008 ◽  
Vol 108 (1) ◽  
pp. 149-159 ◽  
Author(s):  
Kenichiro Muraoka ◽  
Tetsuro Shingo ◽  
Takao Yasuhara ◽  
Masahiro Kameda ◽  
Wen Ji Yuen ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Rat Model ◽  
Fluorescent Protein ◽  
Therapeutic Potential ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Therapeutic Effects ◽  
Adenoviral Infection

Object The therapeutic effects of adult and embryonic neural precursor cells (NPCs) were evaluated and their therapeutic potential compared in a rat model of Parkinson disease. Methods Adult NPCs were obtained from the subventricular zone and embryonic NPCs were taken from the ganglionic eminence of 14-day-old embryos. Each NPC type was cultured with epidermal growth factor. The in vitro neuronal differentiation rate of adult NPCs was approximately equivalent to that of embryonic NPCs after two passages. Next, the NPCs were transfected with either green fluorescent protein or glial cell line–derived neurotrophic factor (GDNF) by adenoviral infection and transplanted into the striata in a rat model of Parkinson disease (PD) induced by unilateral intrastriatal injection of 6-hydroxydopamine. An amphetamine-induced rotation test was used to evaluate rat behavioral improvement, and immunohistochemical analysis was performed to compare grafted cell survival, differentiation, and host tissue changes. Results The rats with GDNF-transfected NPCs had significantly fewer amphetamine-induced rotations and less histological damage. Except for the proportion of surviving grafted cells, there were no significant differences between adult and embryonic NPCs. Conclusions Adult and embryonic NPCs have a comparable therapeutic potential in a rat model of PD.

scholarly journals Prolonged cultivation of hippocampal neural precursor cells shifts their differentiation potential and selects for aneuploid cells

2013 ◽  
Vol 394 (12) ◽  
pp. 1623-1636 ◽  
Author(s):  
The Duy Nguyen ◽  
Darius Widera ◽  
Johannes Greiner ◽  
Janine Müller ◽  
Ina Martin ◽  
...  
Keyword(s):  
Cell Types ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Early Passage ◽  
Differentiation Potential ◽  
Developmental Potential ◽  
Prolonged Cultivation ◽  
Tumorigenic Transformation

Abstract Neural precursor cells (NPCs) are lineage-restricted neural stem cells with limited self-renewal, giving rise to a broad range of neural cell types such as neurons, astrocytes, and oligodendrocytes. Despite this developmental potential, the differentiation capacity of NPCs has been controversially discussed concerning the trespassing lineage boundaries, for instance resulting in hematopoietic competence. Assessing their in vitro plasticity, we isolated nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult NPCs were able to form neurospheres, self-renew, and differentiate into neuronal, astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage efficiently gave rise to neuronal cells in a directed differentiation assay, extensively cultivated NPCs revealed reduced potential for ectodermal differentiation. We further observed successful differentiation of long-term cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs underwent a fate switch during culture. NPCs cultivated for more than 12 passages were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore, they showed growth factor-independent proliferation, a hallmark of tumorigenic transformation. In conclusion, our findings substantiate the lineage restriction of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however, in enhanced differentiation potential, which may be attributed to transformation events leading to aneuploid cells.

scholarly journals Multimodal Therapeutic Effects of Neural Precursor Cells Derived from Human-Induced Pluripotent Stem Cells through Episomal Plasmid-Based Reprogramming in a Rodent Model of Ischemic Stroke

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Seung-Hun Oh ◽  
Yong-Woo Jeong ◽  
Wankyu Choi ◽  
Jeong-Eun Noh ◽  
Suji Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Stroke Model ◽  
Intracerebral Transplantation ◽  
Induced Pluripotent

Stem cell therapy is a promising option for treating functional deficits in the stroke-damaged brain. Induced pluripotent stem cells (iPSCs) are attractive sources for cell therapy as they can be efficiently differentiated into neural lineages. Episomal plasmids (EPs) containing reprogramming factors can induce nonviral, integration-free iPSCs. Thus, iPSCs generated by an EP-based reprogramming technique (ep-iPSCs) have an advantage over gene-integrating iPSCs for clinical applications. However, there are few studies regarding the in vivo efficacy of ep-iPSCs. In this study, we investigated the therapeutic potential of intracerebral transplantation of neural precursor cells differentiated from ep-iPSCs (ep-iPSC-NPCs) in a rodent stroke model. The ep-iPSC-NPCs were transplanted intracerebrally in a peri-infarct area in a rodent stroke model. Rats transplanted with fibroblasts and vehicle were used as controls. The ep-iPSC-NPC-transplanted animals exhibited functional improvements in behavioral and electrophysiological tests. A small proportion of ep-iPSC-NPCs were detected up to 12 weeks after transplantation and were differentiated into both neuronal and glial lineages. In addition, transplanted cells promoted endogenous brain repair, presumably via increased subventricular zone neurogenesis, and reduced poststroke inflammation and glial scar formation. Taken together, these results strongly suggest that intracerebral transplantation of ep-iPSC-NPCs is a useful therapeutic option to treat clinical stroke through multimodal therapeutic mechanisms.

scholarly journals Conserved fate and function of ferumoxides-labeled neural precursor cells in vitro and in vivo

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Mikhal E. Cohen ◽  
Naser Muja ◽  
Nina Fainstein ◽  
Jeff W.M. Bulte ◽  
Tamir Ben-Hur
Keyword(s):  
Precursor Cells ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
And Function
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