Immunological Characteristics and Properties of Glial Restricted Progenitors of Mice, Canine Primary Culture Suspensions, and Human QSV40 Immortalized Cell Lines for Prospective Therapies of Neurodegenerative Disorders

Neurodegeneration can be defined as a process in which neuronal structures and functions undergo changes leading to reduced neuronal survival and increased cell death in the central nervous system (CNS). Neuronal degeneration in specific regions of the CNS is a hallmark of many neurodegenerative disorders, and there is reliable proof that neural stem cells bring therapeutic benefits in treatment of neurological lesions. However, effective therapy with neural stem cells is associated with their biological properties. The assessment of immunological properties and comprehensive studies on the biology of glial restricted progenitors (GRP) are necessary prior to the application of these cells in humans. This study provides an in vitro characterization of the QSV40 glial human cell line, as well as murine and canine primary culture suspensions of GRPs and their mature, astrocytic forms using flow cytometry and immunohistochemical staining. Cytokines and chemokines released by GRPs were assessed by Multiplex ELISA. Some immunological differences observed among species suggest the necessity of reconsidering the pre-clinical model, and that careful testing of immunomodulatory strategies is required before cell transplantation into the CNS can be undertaken.

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PTMAc-PEG-PTMAc hydrogel modified by RGDC and hyaluronic acid promotes neural stem cells' survival and differentiation in vitro

RSC Advances ◽

10.1039/c7ra06614g ◽

2017 ◽

Vol 7 (65) ◽

pp. 41098-41104 ◽

Cited By ~ 6

Author(s):

Ruirui Yang ◽

Caixia Xu ◽

Tao Wang ◽

Yuanqi Wang ◽

Jingnan Wang ◽

...

Keyword(s):

Stem Cells ◽

Central Nervous System ◽

Nervous System ◽

Hyaluronic Acid ◽

Neural Stem Cells ◽

Biological Properties ◽

Central Nervous System Injury ◽

Bioactive Molecules

The enhancement of the biological properties of hydrogels by surface modifying with bioactive molecules is of great significance, especially for the treatment of central nervous system injury by combining engrafted cells.

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In vitro characterization of neural stem cells: Functional response to the enteric neurotrophin GDNF and co-culture with human colonic smooth muscle

Gastroenterology ◽

10.1016/s0016-5085(01)80307-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A62-A62

Author(s):

M MICCI ◽

R LEARISH ◽

P PASRICHA

Keyword(s):

Stem Cells ◽

Smooth Muscle ◽

Neural Stem Cells ◽

Functional Response ◽

In Vitro Characterization

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Glial and Neural Stem Cells as New Therapeutic Targets for Neurodegenerative Disorders

10.3389/978-2-88963-741-6 ◽

2020 ◽

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Neurodegenerative Disorders ◽

Therapeutic Targets ◽

New Therapeutic Targets

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Neural Stem Cells to Glial Cells an Important Factor for Brain Injury

Journal of Regenerative Biology and Medicine ◽

10.37191/mapsci-2582-385x-2(3)-025 ◽

2020 ◽

Author(s):

Prithiv K R Kumar

Keyword(s):

Stem Cells ◽

Central Nervous System ◽

Nervous System ◽

Neural Stem Cells ◽

Glial Cells ◽

Brain Injuries ◽

The Body ◽

The Central Nervous System ◽

Near Future

Stem cells have the capacity to differentiate into any type of cell or organ. Stems cell originate from any part of the body, including the brain. Brain cells or rather neural stem cells have the capacitive advantage of differentiating into the central nervous system leading to the formation of neurons and glial cells. Neural stem cells should have a source by editing DNA, or by mixings chemical enzymes of iPSCs. By this method, a limitless number of neuron stem cells can be obtained. Increase in supply of NSCs help in repairing glial cells which in-turn heal the central nervous system. Generally, brain injuries cause motor and sensory deficits leading to stroke. With all trials from novel therapeutic methods to enhanced rehabilitation time, the economy and quality of life is suppressed. Only PSCs have proven effective for grafting cells into NSCs. Neurons derived from stem cells is the only challenge that limits in-vitro usage in the near future.

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Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation

BMC Molecular and Cell Biology ◽

10.1186/s12860-021-00343-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Emilia Solomon ◽

Katie Davis-Anderson ◽

Blake Hovde ◽

Sofiya Micheva-Viteva ◽

Jennifer Foster Harris ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Motor Neuron ◽

Motor Neurons ◽

Acetylcholine Receptors ◽

Gene Networks ◽

Spinal Cord Injuries ◽

Regulatory Gene ◽

Transcriptome Profile

Abstract Background Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities. Results Employing RNA-seq technology, we identified and characterized gene regulatory networks triggered by in vitro chemical reprogramming of iPSC into cells with the molecular features of motor neurons (MNs) whose function in vivo is to innervate effector organs. We present meta-transcriptome signatures of 5 cell types: iPSCs, neural stem cells, motor neuron progenitors, early motor neurons, and mature motor neurons. In strict response to the chemical stimuli, along the MN differentiation axis we observed temporal downregulation of tumor growth factor-β signaling pathway and consistent activation of sonic hedgehog, Wnt/β-catenin, and Notch signaling. Together with gene networks defining neuronal differentiation (neurogenin 2, microtubule-associated protein 2, Pax6, and neuropilin-1), we observed steady accumulation of motor neuron-specific regulatory genes, including Islet-1 and homeobox protein HB9. Interestingly, transcriptome profiling of the differentiation process showed that Ca2+ signaling through cAMP and LPC was downregulated during the conversion of the iPSC to neural stem cells and key regulatory gene activity of the pathway remained inhibited until later stages of motor neuron formation. Pathways shaping the neuronal development and function were well-represented in the early motor neuron cells including, neuroactive ligand-receptor interactions, axon guidance, and the cholinergic synapse formation. A notable hallmark of our in vitro motor neuron maturation in monoculture was the activation of genes encoding G-coupled muscarinic acetylcholine receptors and downregulation of the ionotropic nicotinic acetylcholine receptors expression. We observed the formation of functional neuronal networks as spontaneous oscillations in the extracellular action potentials recorded on multi-electrode array chip after 20 days of differentiation. Conclusions Detailed transcriptome profile of each developmental step from iPSC to motor neuron driven by chemical induction provides the guidelines to novel therapeutic approaches in the re-construction efforts of muscle innervation.

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Enhanced neural differentiation of neural stem cells by sustained release of Shh from TG2 gene-modified EMSC co-culture in vitro

Amino Acids ◽

10.1007/s00726-020-02918-0 ◽

2020 ◽

Author(s):

Wentao Shi ◽

Lu Bian ◽

Demin Lv ◽

Shiqi Bi ◽

Yao Dai ◽

...

Keyword(s):

Stem Cells ◽

Sustained Release ◽

Neural Stem Cells ◽

Neural Differentiation ◽

Culture In Vitro

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EXTH-07. TUMOR-HOMING INDUCED NEURAL STEM CELLS SECRETING A CYTOTOXIC PAYLOAD AS AN ADJUVANT TREATMENT FOR NON-SMALL CELL LUNG CANCER BRAIN METASTASES

Neuro-Oncology ◽

10.1093/neuonc/noaa215.361 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii88-ii88

Author(s):

Alison Mercer-Smith ◽

Wulin Jiang ◽

Alain Valdivia ◽

Juli Bago ◽

Scott Floyd ◽

...

Keyword(s):

Stem Cells ◽

Brain Metastases ◽

Neural Stem Cells ◽

Adjuvant Treatment ◽

Small Cell ◽

Small Cell Lung ◽

Tumor Homing ◽

Induced Neural Stem Cells

Abstract INTRODUCTION Non-small cell lung cancer (NSCLC) is the most common cancer to form brain metastases. Radiation treatment is standard-of-care, but recurrence is still observed in 40% of patients. An adjuvant treatment is desperately needed to track down and kill tumor remnants after radiation. Tumoritropic neural stem cells (NSCs) that can home to and deliver a cytotoxic payload offer potential as such an adjuvant treatment. Here we show the transdifferentiation of human fibroblasts into tumor-homing induced neural stem cells (hiNSCs) that secrete the cytotoxic protein TRAIL (hiNSC-TRAIL) and explore the use of hiNSC-TRAIL to treat NSCLC brain metastases. METHODS To determine the migratory capacity of hiNSCs, hiNSCs were infused intracerebroventricularly (ICV) into mice bearing established bilateral NSCLC H460 brain tumors. hiNSC accumulation at tumor foci was monitored using bioluminescent imaging and post-mortem fluorescent analysis. To determine synergistic effects of radiation with TRAIL on NSCLC, we performed in vitro co-culture assays and isobologram analysis. In vivo, efficacy was determined by tracking the progression and survival of mice bearing intracranial H460 treated with hiNSC-TRAIL alone or in combination with 2 Gy radiation. RESULTS/CONCLUSION Following ICV infusion, hiNSCs persisted in the brain for > 1 week and migrated from the ventricles to colocalize with bilateral tumor foci. In vitro, viability assays and isobologram analysis revealed the combination treatment of hiNSC-TRAIL and 2 Gy radiation induced synergistic killing (combination index=0.64). In vivo, hiNSC-TRAIL/radiation combination therapy reduced tumor volumes > 90% compared to control-treated animals while radiation-only and hiNSC-TRAIL-only treated mice showed 21% and 52% reduced volumes, respectively. Dual-treatment extended survival 40%, increasing survival from a median of 20 days in controls to 28 days in the treatment group. These results suggest hiNSC-TRAIL can improve radiation therapy for NSCLC brain metastases and could potentially improve outcomes for patients suffering from this aggressive form of cancer.

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Neural stem cells: involvement in adult neurogenesis and CNS repair

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2008.2264 ◽

2008 ◽

Vol 363 (1500) ◽

pp. 2111-2122 ◽

Cited By ~ 71

Author(s):

Hideyuki Okano ◽

Kazunobu Sawamoto

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Cell Transplantation ◽

Adult Neurogenesis ◽

Embryonic Stem ◽

Adult Brain ◽

Therapeutic Interventions ◽

Cell Transplantation Therapy ◽

Transplantation Therapy

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.

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