Silencing of MEKK2/MEKK3 Pathway Protects Against Spinal Cord Injury by Regulating Neural Progenitor Cell Differentiation via Activation of Hedgehog Pathway and Disruption of JNK Pathway

2019 ◽  
Author(s):  
Ya-Dong Zhang ◽  
Zhong-Sheng Zhu ◽  
Zheng-Wei Deng ◽  
Yan-Long Kong ◽  
Jing Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Differentiation ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Hedgehog Pathway ◽  
Jnk Pathway ◽  
Cord Injury

scholarly journals Origins of Neural Progenitor Cell-Derived Axons Projecting Caudally after Spinal Cord Injury

2019 ◽  
Vol 13 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Paul Lu ◽  
Walace Gomes-Leal ◽  
Selin Anil ◽  
Gabriel Dobkins ◽  
J. Russell Huie ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Cord Injury

scholarly journals Regeneration of Corticospinal Axons into Neural Progenitor Cell Grafts After Spinal Cord Injury

2020 ◽  
Vol 15 ◽  
pp. 263310552097400
Author(s):  
Gunnar HD Poplawski ◽  
Mark H Tuszynski
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Spinal Cord Injuries ◽  
Axon Regeneration ◽  
Stem Cell Differentiation ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Cord Injury

Spinal cord injuries leave patients with lifelong paralysis. To date, there are no therapies that promote the critical step required for the recovery of voluntary motor function: corticospinal axon regeneration. Spinal cord-derived neural progenitor cell (NPC) grafts integrate into the injured host spinal cord, enable robust corticospinal axon regeneration, and restore forelimb function following spinal cord injury in rodents. Consequently, engineered stem cell differentiation and transplantation techniques harbor promising potential for the design and implementation of therapies promoting corticospinal axon regeneration. However, in order to optimize the outcome of clinical trials, it is critical to fully understand the cellular and molecular mechanisms underlying this regeneration. Our recent study highlights the unexpected intrinsic potential of corticospinal neurons to regenerate and allows us to investigate new hypotheses exploiting this newly discovered potential.

Optimizing fibrin hydrogel toward effective neural progenitor cell delivery in spinal cord injury

2021 ◽  
Author(s):  
Tara Sudhadevi ◽  
Harikrishnan Vijayakumar Sreelatha ◽  
Easwer V Hariharan ◽  
Samavedam Sandhyamani ◽  
Lissy K Krishnan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Immune Response ◽  
Progenitor Cell ◽  
Cell Attachment ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Cell Delivery ◽  
Cord Injury

Abstract Transplantation of neural progenitor cell (NPC) possessing the potential to differentiate into neurons may guard against spinal cord injury (SCI)- associated neuronal trauma. We propose that autologous-like NPC may reduce post-transplant immune response. The study used the rat SCI model to prove this concept. For isolation and expansion of rat NPC for cell-based SCI therapy, the in vitro protocol standardized with human NPC seemed suitable. The primary aim of this study is to select a cell/neural tissue-compatible biomaterial for improving NPC survival in vivo. The composition of the fibrin hydrogel is adjusted to obtain degradable, porous, and robust fibrin strands for supporting neural cell attachment, migration, and tissue regeneration. This study employed NPC culture to evaluate the cytocompatibility and suitability of the hydrogel, composed by adding graded concentrations of thrombin to a fixed fibrinogen concentration. The microstructure evaluation by scanning electron microscope guided the selection of a suitable composition for delivering the embedded cells. On adding more thrombin, fibrinogen clotted quickly but reduced porosity, pore size, and fiber strand thickness. The high activity of thrombin also affected NPC morphology and the in vitro cell survival. The selected hydrogel carried viable NPC and retained them at the injury site post-transplantation. The fibrin hydrogel played a protective role throughout the transfer process by providing cell attachment sites and survival signals. The fibrin and NPC together regulated the immune response at the SCI site reducing ED1+ve/ED2+ve macrophages in the early period of 8 to 16 days after injury. Migration of β-III tubulin+ve neural-like cells into the fibrin-injected control SCI is evident. The continuous use of a non-neurotoxic fibrin matrix could be a convenient strategy for in vitro NPC preparation, minimally invasive cell delivery, and better transplantation outcome.

scholarly journals Calcium Imaging Reveals Host-Graft Synaptic Network Formation in Spinal Cord Injury

2019 ◽  
Author(s):  
S Ceto ◽  
KJ Sekiguchi ◽  
Y Takashima ◽  
A Nimmerjahn ◽  
MH Tuszynski
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Calcium Imaging ◽  
Progenitor Cell ◽  
Neural Progenitor Cell ◽  
Neural Progenitor ◽  
Optogenetic Stimulation ◽  
Cord Injury ◽  
Stimulation Of

SummaryNeural stem/progenitor cell grafts integrate into sites of spinal cord injury (SCI) and form anatomical and electrophysiological neuronal relays across lesions. To determine how grafts become synaptically organized and connect with host systems, we performed calcium imaging of neural progenitor cell grafts within sites of SCI, using both in vivo imaging and spinal cord slices. Stem cell grafts organize into localized synaptic networks that are spontaneously active. Following optogenetic stimulation of host corticospinal tract axons regenerating into grafts, distinct and segregated neuronal networks respond throughout the graft. Moreover, optogenetic stimulation of graft axons extending out from the lesion into the denervated spinal cord also trigger responses in local host neuronal networks. In vivo imaging reveals that behavioral stimulation of host elicits focal synaptic responses within grafts. Thus, remarkably, neural progenitor cell grafts form functional synaptic subnetworks in patterns paralleling the normal spinal cord.

scholarly journals Silencing of the MEKK2/MEKK3 Pathway Protects against Spinal Cord Injury via the Hedgehog Pathway and the JNK Pathway

2019 ◽  
Vol 17 ◽  
pp. 578-589 ◽  
Author(s):  
Yan-Long Kong ◽  
Yi-Fei Wang ◽  
Zhong-Sheng Zhu ◽  
Zheng-Wei Deng ◽  
Jing Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Hedgehog Pathway ◽  
Jnk Pathway ◽  
Cord Injury

scholarly journals Biomimetic hydrogels direct spinal progenitor cell differentiation and promote functional recovery after spinal cord injury

2018 ◽  
Vol 15 (2) ◽  
pp. 025004 ◽  
Author(s):  
Sydney A Geissler ◽  
Alexandra L Sabin ◽  
Rachel R Besser ◽  
Olivia M Gooden ◽  
Bryce D Shirk ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Differentiation ◽  
Functional Recovery ◽  
Progenitor Cell ◽  
Cord Injury
Sign in / Sign up

Export Citation Format

Share Document