Neural Stem Cells in Stroke: Intracerebral Approaches

Manley, Nathan C.; Azevedo-Pereira, Ricardo Luiz; Bliss, Tonya; Steinberg, Gary K.

doi:10.1007/978-3-319-15063-5_7

Cited by 9 publications

(12 citation statements)

References 99 publications

(124 reference statements)

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“…After the establishment of cultured embryonic stem cell (ESC) lines (Thomson, ), several groups have successfully developed ESC‐derived long‐term expandable NSCs (ESC‐NSCs) from multiple species including human (Elkabetz et al, ), mouse (Lee, Lumelsky, Studer, Auerbach, & McKay, ), and primate (Ikeda et al, ). The therapeutic use of ESC‐NSCs could be advantageous over NSCs of fetal origin due to the theoretically limitless source of immortal ESCs in which to scale‐up cell manufacturing to meet the clinical demand (Manley, Azevedo‐Pereira, Bliss, & Steinberg, ). To date, there have been no clinical trials testing ESC‐NSCs for stroke.…”

Section: Sources Of Neural Stem Cellsmentioning

confidence: 99%

“…The brain is typically immunoprivileged, yet in the stroke environment the BBB is compromised and undergoes dynamic changes in permeability allowing for infiltration of systemic immune cells. This has raised questions pertaining to the immune system response to transplantation of allogeneic NSC lines in stroke and the potential need for autologous iPSC‐NSCs to overcome this response (Manley et al, ). However, the amount of time needed to generate and safety test iPSC‐NSCs with current technologies is likely beyond the treatment window of therapeutic efficacy if one expects large‐scale cell replacement.…”

Section: Clinical Considerations For Translationmentioning

confidence: 99%

“…The brain is typically immunoprivileged, yet in the stroke environment the BBB is compromised and undergoes dynamic changes in permeability allowing for infiltration of systemic immune cells. This has raised questions pertaining to the immune system response to transplantation of allogeneic NSC lines in stroke and the potential need for autologous iPSC-NSCs to overcome this response (Manley et al, 2015). (Sandu, Buga, Uzoni, Petcu, & Popa-Wagner, 2015).…”

Section: Clini C Al Con S Ider Ati On S For Tr An S L Ati Onmentioning

confidence: 99%

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Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function

2019

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Introduction Neural stem cells (NSCs) have demonstrated multimodal therapeutic function for stroke, which is the leading cause of long‐term disability and the second leading cause of death worldwide. In preclinical stroke models, NSCs have been shown to modulate inflammation, foster neuroplasticity and neural reorganization, promote angiogenesis, and act as a cellular replacement by differentiating into mature neural cell types. However, there are several key technical questions to address before NSC therapy can be applied to the clinical setting on a large scale. Purpose of Review In this review, we will discuss the various sources of NSCs, their therapeutic modes of action to enhance stroke recovery, and considerations for the clinical translation of NSC therapies. Understanding the key factors involved in NSC‐mediated tissue recovery and addressing the current translational barriers may lead to clinical success of NSC therapy and a first‐in‐class restorative therapy for stroke patients.

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Section: Sources Of Neural Stem Cellsmentioning

confidence: 99%

Section: Clinical Considerations For Translationmentioning

confidence: 99%

“…The brain is typically immunoprivileged, yet in the stroke environment the BBB is compromised and undergoes dynamic changes in permeability allowing for infiltration of systemic immune cells. This has raised questions pertaining to the immune system response to transplantation of allogeneic NSC lines in stroke and the potential need for autologous iPSC-NSCs to overcome this response (Manley et al, 2015). (Sandu, Buga, Uzoni, Petcu, & Popa-Wagner, 2015).…”

Section: Clini C Al Con S Ider Ati On S For Tr An S L Ati Onmentioning

confidence: 99%

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Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function

2019

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“…iPSC-derived NSCs are being widely studied for treating various human neuronal diseases5859. These NSCs could survive, mature and outgrowth long nerve fibers in rodent model of spinal cord injuries60.…”

Section: Discussionmentioning

confidence: 99%

An Integrated Miniature Bioprocessing for Personalized Human Induced Pluripotent Stem Cell Expansion and Differentiation into Neural Stem Cells

Lin

Lei

2017

Sci Rep

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Human induced pluripotent stem cells (iPSCs) are ideal cell sources for personalized cell therapies since they can be expanded to generate large numbers of cells and differentiated into presumably all the cell types of the human body in vitro. In addition, patient specific iPSC-derived cells induce minimal or no immune response in vivo. However, with current cell culture technologies and bioprocessing, the cost for biomanufacturing clinical-grade patient specific iPSCs and their derivatives are very high and not affordable for majority of patients. In this paper, we explored the use of closed and miniature cell culture device for biomanufacturing patient specific neural stem cells (NSCs) from iPSCs. We demonstrated that, with the assist of a thermoreversible hydrogel scaffold, the bioprocessing including iPSC expansion, iPSC differentiation into NSCs, the subsequent depletion of undifferentiated iPSCs from the NSCs, and concentrating and transporting the purified NSCs to the surgery room, could be integrated and completed within two closed 15 ml conical tubes.

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“…Correlation of FA values with existing clinical scales can help develop new objective scales for assessing the integrity of tracts during the course of a disease and its treatment. Neurorehabilitation physicians, by contrast to neurosurgeons, can focus more on tract volume measurements in order to personalize physiotherapy schedules and timing and improve the accuracy of prognosis.4.1.2 Clinical translation of novel therapeutics in neuroscience.Neurologists, neurorehabilitation physicians and neural engineers are currently moving toward clinical translation of neural repair and neuroprotection strategies for CNS trauma and disease, such as TBI(Aertker et al 2016), stroke(Manley et al 2015), ALS(Petrou et al 2016) and SCI(Lu et al 2016).Nevertheless, in order to quantify and assess the effects of such novel therapeutics in neurological patients, non-invasive, reliable in vivo techniques are a key aspect of progressing to a safe clinical translation. Our method could easily be implemented in clinical studies in order to assess new therapeutic interventions that are progressing to clinical trials.…”

mentioning

confidence: 99%

Individual variations of the human corticospinal tract and its hand-related motor fibers using diffusion MRI tractography

Dalamagkas

Tsintou

Rathi

et al. 2018

Preprint

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The corticospinal tract (CST) is one of the most well-studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available.However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we proposed a novel method, using manually-drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heatmaps from 37 subjects for both the aforementioned tracts, which could be utilized as reference for clinicians to explore neuropathology in both trauma and disease states.Graphical abstract 1

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Neural Stem Cells in Stroke: Intracerebral Approaches

Cited by 9 publications

References 99 publications

Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function

Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function

An Integrated Miniature Bioprocessing for Personalized Human Induced Pluripotent Stem Cell Expansion and Differentiation into Neural Stem Cells

Individual variations of the human corticospinal tract and its hand-related motor fibers using diffusion MRI tractography

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