scholarly journals Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks

Nano Research ◽  
2019 ◽  
Vol 12 (11) ◽  
pp. 2894-2899 ◽  
Author(s):  
Gabriela S. Lorite ◽  
Laura Ylä-Outinen ◽  
Lauriane Janssen ◽  
Olli Pitkänen ◽  
Tiina Joki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Carbon Nanotube ◽  
Spinal Cord Injuries ◽  
Three Dimensional ◽  
Cell Types ◽  
Therapeutic Effects ◽  
Guided Growth ◽  
Human Neural Stem Cells ◽  
Cell Network ◽  
Human Neurons

Abstract New strategies for spatially controlled growth of human neurons may provide viable solutions to treat and recover peripheral or spinal cord injuries. While topography cues are known to promote attachment and direct proliferation of many cell types, guided outgrowth of human neurites has been found difficult to achieve so far. Here, three-dimensional (3D) micropatterned carbon nanotube (CNT) templates are used to effectively direct human neurite stem cell growth. By exploiting the mechanical flexibility, electrically conductivity and texture of the 3D CNT micropillars, a perfect environment is created to achieve specific guidance of human neurites, which may lead to enhanced therapeutic effects within the injured spinal cord or peripheral nerves. It is found that the 3D CNT micropillars grant excellent anchoring for adjacent neurites to form seamless neuronal networks that can be grown to any arbitrary shape and size. Apart from clear practical relevance in regenerative medicine, these results using the CNT based templates on Si chips also can pave the road for new types of microelectrode arrays to study cell network electrophysiology.

scholarly journals Multifunctionalized hydrogels foster hNSC maturation in 3D cultures and neural regeneration in spinal cord injuries

2019 ◽  
Vol 116 (15) ◽  
pp. 7483-7492 ◽  
Author(s):  
Amanda Marchini ◽  
Andrea Raspa ◽  
Raffaele Pugliese ◽  
Marina Abd El Malek ◽  
Valentina Pastori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Culture Media ◽  
Three Dimensional ◽  
Cholinergic Neurons ◽  
Good Manufacturing Practice ◽  
Neural Regeneration ◽  
Neuronal Markers

Three-dimensional cell cultures are leading the way to the fabrication of tissue-like constructs useful to developmental biology and pharmaceutical screenings. However, their reproducibility and translational potential have been limited by biomaterial and culture media compositions, as well as cellular sources. We developed a construct comprising synthetic multifunctionalized hydrogels, serum-free media, and densely seeded good manufacturing practice protocol-grade human neural stem cells (hNSC). We tracked hNSC proliferation, differentiation, and maturation into GABAergic, glutamatergic, and cholinergic neurons, showing entangled electrically active neural networks. The neuroregenerative potential of the “engineered tissue” was assessed in spinal cord injuries, where hNSC-derived progenitors and predifferentiated hNSC progeny, embedded in multifunctionalized hydrogels, were implanted. All implants decreased astrogliosis and lowered the immune response, but scaffolds with predifferentiated hNSCs showed higher percentages of neuronal markers, better hNSC engraftment, and improved behavioral recovery. Our hNSC-construct enables the formation of 3D functional neuronal networks in vitro, allowing novel strategies for hNSC therapies in vivo.

scholarly journals Stem Cell Neurodevelopmental Solutions for Restorative Treatments of the Human Trunk and Spine

2021 ◽  
Vol 15 ◽  
Author(s):  
Zachary T. Olmsted ◽  
Janet L. Paluh
Keyword(s):  
Spinal Cord ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Spinal Cord Injuries ◽  
Full Range ◽  
Cell Types ◽  
Near Term ◽  
Developmental Principles ◽  
Spine Disorders ◽  
Cell Community

The ability to reliably repair spinal cord injuries (SCI) will be one of the greatest human achievements realized in regenerative medicine. Until recently, the cellular path to this goal has been challenging. However, as detailed developmental principles are revealed in mouse and human models, their application in the stem cell community brings trunk and spine embryology into efforts to advance human regenerative medicine. New models of posterior embryo development identify neuromesodermal progenitors (NMPs) as a major bifurcation point in generating the spinal cord and somites and is leading to production of cell types with the full range of axial identities critical for repair of trunk and spine disorders. This is coupled with organoid technologies including assembloids, circuitoids, and gastruloids. We describe a paradigm for applying developmental principles towards the goal of cell-based restorative therapies to enable reproducible and effective near-term clinical interventions.

scholarly journals Considering the Cellular Composition of Olfactory Ensheathing Cell Transplants for Spinal Cord Injury Repair: A Review of the Literature

2021 ◽  
Vol 15 ◽  
Author(s):  
Mahjabeen Miah ◽  
Patrizia Ferretti ◽  
David Choi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Cell Types ◽  
Convincing Evidence ◽  
Therapeutic Outcome ◽  
Olfactory Ensheathing Cell ◽  
Cell Composition ◽  
Cord Injury ◽  
Cell Transplants ◽  
Different Cell Types

Olfactory ensheathing cells (OECs) are specialized glia cells of the olfactory system that support the continual regeneration of olfactory neurons throughout adulthood. Owing to their pro-regenerative properties, OECs have been transplanted in animal models of spinal cord injuries (SCI) and trialed in clinical studies on SCI patients. Although these studies have provided convincing evidence to support the continued development of OEC transplantation as a treatment option for the repair of SCI, discrepancies in the reported outcome has shown that OEC transplantation requires further improvement. Much of the variability in the reparative potential of OEC transplants is due to the variations in the cell composition of transplants between studies. As a result, the optimal cell preparation is currently a subject of debate. Here we review, the characterization as well as the effect of the cell composition of olfactory cell transplantation on therapeutic outcome in SCI. Firstly, we summarize and review the cell composition of olfactory cell preparations across the different species studied prior to transplantation. Since the purity of cells in olfactory transplants might affect the study outcome we also examine the effect of the proportions of OECs and the different cell types identified in the transplant on neuroregeneration. Finally, we consider the effect of the yield of cells on neuroregeneration by assessing the cell dose of transplants on therapeutic outcome.

scholarly journals Three-dimensional aligned nanofibers-hydrogel scaffold for controlled non-viral drug/gene delivery to direct axon regeneration in spinal cord injury treatment

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Lan Huong Nguyen ◽  
Mingyong Gao ◽  
Junquan Lin ◽  
Wutian Wu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Three Dimensional ◽  
Neurological Dysfunction ◽  
Post Injury ◽  
Hydrogel Scaffold ◽  
Cord Injury ◽  
Aligned Nanofibers ◽  
Injury Treatment

Abstract Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment. A hemi-incision model at cervical level 5 in the rat spinal cord was chosen to evaluate the efficacy of this scaffold design. Specifically, aligned axon regeneration was observed as early as one week post-injury. In addition, no excessive inflammatory response and scar tissue formation was triggered. Taken together, our results demonstrate the potential of our scaffold for neural tissue engineering applications.

scholarly journals Artery of Adamkiewicz and the clinical repercussion of its lesion in thoracoabdominal surgeries: a systematic review

2021 ◽  
Vol 1 (4) ◽  
pp. 9-21
Author(s):  
Idna Lara Goes de Sena ◽  
Maria Regina Cardoso Linhares Oliveira Lima ◽  
Lia de Oliveira Jereissati ◽  
Rafaella Iughetti da Costa ◽  
Victor Oliveira Araújo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Spinal Cord Ischemia ◽  
Three Dimensional ◽  
Clinical Importance ◽  
Dimensional Network ◽  
Adamkiewicz Artery ◽  
Artery Of Adamkiewicz ◽  
Pass Through ◽  
Preoperative Procedure

The knowledge of the spinal cord irrigation is important for the therapeutic planning of aortic pathologies; however, its vasculature is complex due to the caliber of its arteries that pass through a three-dimensional network with great anatomical variability. Its clinical importance is evidenced during the preoperative procedure of thoracic and thoracoabdominal aortic surgeries, because its identification is essential for the prevention of spinal cord injuries. This study consists of a literature review, in which searches were conducted in the databases - Bireme, Science Direct, Pubmed and Lilacs. Articles published between 1999 and 2020, written in English, Portuguese or Spanish, were selected. The search was conducted using the descriptors Anatomy, Spinal Cord Irrigation and Spinal Cord Ischemia. The Adamkiewicz artery is the main artery responsible for the arterial supply to the lower part of the spinal cord. Thus, paraplegia is a complication of this type of surgical approach resulting from ischemic suffering of the spinal cord during the process. Therefore, further study on these factors should be encouraged, because the preservation of this vessel is relevant given the search for protection of the spinal cord and the maintenance of its functions in this type of procedure.

scholarly journals biPACT: a method for three-dimensional visualization of mouse spinal cord circuits of long segments with high resolution

2021 ◽  
Author(s):  
Katsuyuki Nakanishi ◽  
Munehisa Shinozaki ◽  
Narihito Nagoshi ◽  
Masaya Nakamura ◽  
Hideyuki Okano
Keyword(s):  
Spinal Cord ◽  
High Resolution ◽  
Spinal Cord Injuries ◽  
Neural Circuit ◽  
Three Dimensional ◽  
Special Equipment ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Wide Range ◽  
High Resolution Images

Background: The spatial complexity of neuronal circuits in the central nervous system is an hurdle in understanding and treating brain and spinal cord injuries. Although several methods have recently been developed to render the spinal cord transparent and label specific neural circuits, three-dimensional visualization of long segments of spinal cord with high resolution remains challenging. New Method: We have established a method that combines tissue staining of neuronal tracts traced with biotinylated dextran amine (BDA) and a modified passive clarity clearing protocol. Results: BDA was injected into the unilateral sensorimotor cortex of a mouse model of thoracic spinal cord contusional injury. Ten days later, the spinal cord was removed and immersed first in staining solution and then in hydrogel solution. The spinal cord was then sealed with a syringe and underwent gelation process, followed by clearing with clearing solution and observation solution. Staining and clearing took a total of two weeks. The samples were observed with a lightsheet microscope, and three-dimensional reconstruction was performed with ImageJ software. With the lightsheet microscope, high resolution-images comparable with tissue sections were obtained continuously and circumferentially. By tiling, it was possible to obtain high-resolution images of long segments of the spinal cord, in which each fiber could be traced. The tissue could be easily re-stained in case of fading. Comparison with Existing Methods: The present method does not require special equipment, can label specific circuits without genetic technology, and re-staining rounds can be easily implemented. It enables to visualize specific neural circuit of long spinal cord segments with high resolution up to individual nerve fiber. Conclusions: By using simple neural labeling, staining, and transparency methods, it was possible to acquire a wide range of high-resolution three-dimensional images of the spinal cord.

scholarly journals Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Euler Moraes Penha ◽  
Cássio Santana Meira ◽  
Elisalva Teixeira Guimarães ◽  
Marcus Vinícius Pinheiro Mendonça ◽  
Faye Alice Gravely ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Magnetic Resonance ◽  
Spinal Cord Injuries ◽  
Autologous Bone Marrow ◽  
Therapeutic Effects ◽  
Cord Injury

The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were culturedin vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury.

scholarly journals Simultaneous submicrometric 3D imaging of the micro-vascular network and the neuronal system in a mouse spinal cord

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Michela Fratini ◽  
Inna Bukreeva ◽  
Gaetano Campi ◽  
Francesco Brun ◽  
Giuliana Tromba ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Ex Vivo ◽  
Clinical Investigation ◽  
Three Dimensional ◽  
Nerve Fibers ◽  
Neuronal System ◽  
Mouse Spinal Cord ◽  
Spatial Coverage ◽  
Neuronal Systems

Abstract Faults in vascular (VN) and neuronal networks of spinal cord are responsible for serious neurodegenerative pathologies. Because of inadequate investigation tools, the lacking knowledge of the complete fine structure of VN and neuronal system represents a crucial problem. Conventional 2D imaging yields incomplete spatial coverage leading to possible data misinterpretation, whereas standard 3D computed tomography imaging achieves insufficient resolution and contrast. We show that X-ray high-resolution phase-contrast tomography allows the simultaneous visualization of three-dimensional VN and neuronal systems of ex-vivo mouse spinal cord at scales spanning from millimeters to hundreds of nanometers, with nor contrast agent nor sectioning and neither destructive sample-preparation. We image both the 3D distribution of micro-capillary network and the micrometric nerve fibers, axon-bundles and neuron soma. Our approach is very suitable for pre-clinical investigation of neurodegenerative pathologies and spinal-cord-injuries, in particular to resolve the entangled relationship between VN and neuronal system.

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