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

Lu, Paul; Gomes-Leal, Walace; Anil, Selin; Dobkins, Gabriel; Huie, J. Russell; Ferguson, Adam R.; Graham, Lori; Tuszynski, Mark H.

doi:10.1016/j.stemcr.2019.05.011

Cited by 22 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the density of ChrimsonR-tdTomato-labeled axons varied throughout different regions of grafts, as previously observed (Dulin et al, 2018;Kumamaru et al, 2019), response strength to corticospinal stimulation in a given cell was uncorrelated with the brightness of tdTomato signal in the corresponding region of interest (n = 68 cells in N = 3 animals; response strength and tdTomato brightness normalized to their respective maximum in each imaging field; Figure S5D-S5E). Thus, graft cells are activated by corticospinal stimulation in all regions of grafts, including the caudal regions of grafts that contains the preponderance of graft neurons that extend axons into the host spinal cord below the injury (Lu et al, 2019).…”

Section: Temporal Spread Of Activity Within Graft Neuronal Assembliesmentioning

confidence: 99%

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury

et al. 2020

View full text Add to dashboard Cite

Neural 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.

show abstract

Section: Temporal Spread Of Activity Within Graft Neuronal Assembliesmentioning

confidence: 99%

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A number of previous studies emphasized the synaptic connection between graft and host neurons and implied the necessity of integrating graft neurons into host neuronal circuits ( Ceto et al., 2020 ; Kadoya et al., 2016 ; Lu et al., 2012 , 2019 ). For instance, our previous study transplanting neurogenic NS/PCs led to a further functional improvement of host animals, which suggested the potency of robust neuronal differentiation ( Okubo et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Modulation by DREADD reveals the therapeutic effect of human iPSC-derived neuronal activity on functional recovery after spinal cord injury

et al. 2022

View full text Add to dashboard Cite

Transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) is considered to be a promising therapy for spinal cord injury (SCI) and will soon be translated to the clinical phase. However, how grafted neuronal activity influences functional recovery has not been fully elucidated. Here, we show the locomotor functional changes caused by inhibiting the neuronal activity of grafted cells using a designer receptor exclusively activated by designer drugs (DREADD). In vitro analyses of inhibitory DREADD (hM4Di)-expressing cells demonstrated the precise inhibition of neuronal activity via administration of clozapine N-oxide. This inhibition led to a significant decrease in locomotor function in SCI mice with cell transplantation, which was exclusively observed following the maturation of grafted neurons. Furthermore, trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results highlight the significance of engrafting functionally competent neurons by hiPSC-NS/PC transplantation for sufficient recovery from SCI.

show abstract

“…In recent years, stem cell transplantation is considered an appealing treatment approach for CNS diseases (Curtis et al, 2018; Mothe & Tator, 2013). Different stem cells have been used in many SCI studies (Cofano et al, 2019; Hakim et al, 2019; Lu et al, 2019; Paspala et al, 2009); however, among them, NS/PCs seem to be a preferable candidate for the nervous system due to their CNS origin and their differentiation capacity into neuronal and glial cells (Weiss et al, 1996). Furthermore, they suppress the inflammatory reaction, secrete neurotrophic factors and subsequently preserve damaged cells in the injury site (Mothe & Tator, 2012; Pluchino et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Local delivery of fingolimod through PLGA nanoparticles and PuraMatrix‐embedded neural precursor cells promote motor function recovery and tissue repair in spinal cord injury

Zeraatpisheh

Mirzaei

Nami

et al. 2021

Eur J of Neuroscience

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a devastating clinical problem that can lead to permanent motor dysfunction. Fingolimod (FTY720) is a sphingosine structural analogue, and recently, its therapeutic benefits in SCI have been reported. The present study aimed to evaluate the therapeutic efficacy of fingolimod‐incorporated poly lactic‐co‐glycolic acid (PLGA) nanoparticles (nanofingolimod) delivered locally together with neural stem/progenitor cells (NS/PCs) transplantation in a mouse model of contusive acute SCI. Fingolimod was encapsulated in PLGA nanoparticles by the emulsion–evaporation method. Mouse NS/PCs were harvested and cultured from embryonic Day 14 (E14) ganglionic eminences. Induction of SCI was followed by the intrathecal delivery of nanofingolimod with and without intralesional transplantation of PuraMatrix‐encapsulated NS/PCs. Functional recovery, injury size and the fate of the transplanted cells were evaluated after 28 days. The nanofingolimod particles represented spherical morphology. The entrapment efficiency determined by UV–visible spectroscopy was approximately 90%, and the drug content of fingolimod loaded nanoparticles was 13%. About 68% of encapsulated fingolimod was slowly released within 10 days. Local delivery of nanofingolimod in combination with NS/PCs transplantation led to a stronger improvement in neurological functions and minimized tissue damage. Furthermore, co‐administration of nanofingolimod and NS/PCs not only increased the survival of transplanted cells but also promoted their fate towards more oligodendrocytic phenotype. Our data suggest that local release of nanofingolimod in combination with three‐dimensional (3D) transplantation of NS/PCs in the acute phase of SCI could be a promising approach to restore the damaged tissues and improve neurological functions.

show abstract

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

Cited by 22 publications

References 25 publications

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury

Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury

Modulation by DREADD reveals the therapeutic effect of human iPSC-derived neuronal activity on functional recovery after spinal cord injury

Local delivery of fingolimod through PLGA nanoparticles and PuraMatrix‐embedded neural precursor cells promote motor function recovery and tissue repair in spinal cord injury

Contact Info

Product

Resources

About