Biology subjects

Delarue, Q.

Publications and source records attributed to Delarue, Q..

6 recordsLinked to original sources

bioRxiv2025

Repetitive Trans-spinal magnetic stimulation Promotes Repair in Inflammatory Spinal Cord Injury Through Sex-Dependent Immune Modulation

Spinal cord injuries (SCI), whether traumatic or inflammatory such as transverse myelitis (TM), are characterized by severe neuroinflammation, demyelination, and long-term disabilities. Current treatments remain limited, highlighting the need for novel non-invasive therapeutic approaches. Repetitive magnetic stimulation (RMS) has emerged as a promising strategy, but its mechanisms and efficacy in inflammatory contexts remain poorly described. Here, we investigated the effects of RMS applied as trans-spinal RMS (rTSMS) in a mouse model of focal spinal cord demyelination induced by lysophosphatidylcholine (LPC). When applied one day after LPC injection, rTSMS reduced inflammation, demyelination, and fibroglial scar formation, while promoting early locomotor recovery in both sexes. In contrast, when treatment was initiated three days after LPC injection, corresponding to the peak of motor deficits, rTSMS conferred tissue protection and functional benefits only in female mice. RNA sequencing analyses revealed sex-dependent immune modulation: in females, rTSMS primarily regulated adaptive T cell-related pathways, whereas in males, it mainly targeted innate immune responses such as neutrophil activity and phagocytosis. Complementary in vitro experiments using microglial and macrophage cultures further demonstrated that RMS modulates transcriptomic responses differently depending on cell type and inflammatory state. Specifically, RMS attenuated IL-1-induced pro-inflammatory signaling in macrophages and completely abolished these effects in microglia. Altogether, our findings establish rTSMS as a non-invasive therapy capable of reducing neuroinflammation and demyelination in inflammatory SCI, with pronounced sex-dependent effects. By uncovering distinct immune pathways engaged in male and female mice, this study provides mechanistic insights into rTSMS action and opens perspectives for its translational use in neuroinflammatory diseases.

neuroscience↗

bioRxiv2025

Activation of Endogenous Spinal Cord Stem Cell Mediates Recovery Induced by Olfactory Ensheathing Cell Transplantation Following Spinal Cord Injury

Spinal cord injury (SCI) leads to irreversible motor and sensory deficits and currently has no curative treatment. Among the various therapeutic strategies explored, cell transplantation-- using either stem or differentiated cells--has been extensively studied. One of the most promising approaches involves the use of olfactory ensheathing cells (OECs), which have demonstrated unique potential to promote functional recovery and tissue repair following SCI. However, the mechanisms underlying these effects remain poorly understood. In this study, we investigated how OEC transplantation modulates endogenous spinal stem cells, with a particular focus on ependymal cells. Using inducible transgenic mouse lines and fate-mapping approaches, we show that OEC transplantation significantly enhances ependymal cell proliferation and self-renewal both in vivo and in vitro. Moreover, OECs promote astrocytic differentiation of ependymal progeny, which express low levels of inhibitory molecules-- suggesting a supportive role in creating a permissive scar microenvironment. Transcriptomic analyses further revealed that OEC transplantation downregulates genes associated with axonal growth inhibition, thereby contributing to improved neuronal survival. Finally, by using a unique transgenic mouse model in which ependymal cell proliferation is genetically blocked, we demonstrate that the beneficial effects of OEC transplantation depend on ependymal cell activation. Together, these findings establish ependymal cells as essential mediators of the regenerative response induced by OECs. They also highlight a therapeutic strategy based on activating and modulating endogenous stem cells via the transient presence of non-integrating transplanted glial cells. This work contributes to our understanding of SCI repair and supports the clinical potential of OEC-based cell therapies.

neuroscience↗

bioRxiv2025

Altered therapeutic capacities of olfactory ensheathing cells caused by a lesion in an autologous transplantation model for the treatment of spinal cord injury.

Spinal cord injury (SCI) causes irreversible loss of motor, sensory, and autonomic functions and currently has no cure. Beyond local damage, SCI induces systemic inflammation, including cerebral inflammation that impairs neurogenesis. While cell therapies show promising effects in animal models, such as scar reduction and neuroprotection, their benefits in humans remain limited. One key difference lies in the transplantation strategy: animals receive healthy donor cells, whereas humans require autologous transplants. This led us to investigate how the lesion context affects the neuro-reparative potential of olfactory ensheathing cells (OECs) harvested from olfactory bulbs. To this end, we cultured OECs from healthy animals and from animals that had undergone SCI one week earlier. We then transplanted both types of OECs into recipient animals after SCI for therapeutic purposes. Using functional sensory-motor studies, histological and gene expression analyses, we were able to demonstrate for the first time that the lesion negatively affects the therapeutic properties of cells used to treat SCI. Indeed, transplantation of cells from previously injured animals does not modulate the fibrotic and glial scar, or the demyelinated areas at the lesion site, and therefore fails to improve functional recovery; unlike cells derived from healthy donors. Moreover, our in vitro studies show that cells derived from SCI animals secrete pro-inflammatory molecules that promote the polarization of microglia toward a pro-inflammatory phenotype. Altogether, these innovative findings provide new insights into the potential of cell transplantation in the context of autologous therapy after SCI. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=147 HEIGHT=200 SRC="FIGDIR/small/660789v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@2e9b52org.highwire.dtl.DTLVardef@1d75bfaorg.highwire.dtl.DTLVardef@1d7af58org.highwire.dtl.DTLVardef@138f1b8_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Brain inflammation and cognitive decline induced by spinal cord injury can be reversed by spinal cord cell transplants

Spinal cord injuries (SCIs) affect between 250,000 and 500,000 people worldwide each year, most commonly due to road accidents or falls. These injuries result in permanent disabilities, the severity and impact of which are directly related to the extent and location of the injury. Recent studies have also shown that SCIs can lead to cognitive disorders due to inflammation in the brain. From a therapeutic perspective, numerous treatments have been explored, including cell therapy. It has been established that a common mechanism across various cellular transplant models is the modulation of inflammation at the injury site. However, it remains unclear whether the immunomodulatory effects observed in the spinal cord also extend to the brain. To test this hypothesis, we induced SCI in wild-type mice and treated them with transplants of differentiated cells, specifically olfactory ensheathing cells, or stem cells, such as mesenchymal stem cells. Our results demonstrate that both types of transplants can reverse cognitive disorders induced by SCI. Additionally, we found that these cellular transplants modulate brain inflammation and increase neuronal density in the hippocampus. To our knowledge, this is the first study to show that cells transplanted into the spinal cord can modulate the inflammatory response in the brain, thereby reversing the negative effects of injury on brain function following SCI. These findings underscore the complex interactions between the brain and spinal cord under both physiological and pathological conditions.

neuroscience↗

bioRxiv2024

Spinal cord injury: What are the lesion effects on transplanted cells in an autograft model?

AbstractSpinal cord injury (SCI) is a serious pathology of the central nervous system that results in loss of motor, sensory and autonomic functions below the level of the lesion and for which, unfortunately, there is currently no cure. In addition to the loss of function, SCI induces a systemic inflammation that is not confined to the spinal cord and whose effects are increasingly well characterized. In particular, SCI causes cerebral inflammation, which is responsible for the impairment of hippocampal and bulbar neurogenesis. Many therapies have been tested as potential treatments for SCI. In animal models, cell therapies have shown interesting effects such as spinal scar reduction, anti-inflammatory properties, axonal regrowth or neuronal survival, allowing better functional recovery. However, in human studies, their therapeutic capacities are less significant. Beyond obvious differences in pathophysiology and cell culture procedures, a key paradigm of cell transplantation differs between humans and animals. In animal models, transplanted cells are systematically taken from healthy individuals, whereas in humans the immune incompatibility leads to the realization of autologous transplantation. Therefore, we were interested in the lesion effects on the neuro-repairing potential of olfactory ensheathing cells (OECs) harvested from olfactory bulbs. Using functional sensory-motor studies, histological and gene expression analyses, we were able to demonstrate for the first time that the lesion negatively affects the therapeutic properties of cells used to treat SCI. These innovative results shed new light on the future use of cell transplantation in autologous transplantation after SCI.

neuroscience↗

bioRxiv2021

Reaction of ependymal cells to spinal cord injury: a potential role for oncostatin pathway and microglial cells

Ependymal cells with stem cell properties reside in the adult spinal cord around the central canal. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying their activation and their glial-biased differentiation in mammals remain ill-defined. This represents an obstacle to control these cells. We addressed this issue using RNA profiling of ependymal cells before and after injury. We found that these cells activate STAT3 and ERK/MAPK signaling during injury and downregulate cilia-associated genes and FOXJ1, a central transcription factor in ciliogenesis. Conversely, they upregulate 510 genes, six of them more than 20 fold, namely Crym, Ecm1, Ifi202b, Nupr1, Rbp1, Thbs2 and Osmr. OSMR is the receptor for the inflammatory cytokine oncostatin (OSM) and we studied its regulation and role using neurospheres derived from ependymal cells. We found that OSM induces strong OSMR and p-STAT3 expression together with proliferation reduction and astrocytic differentiation. Conversely, production of oligodendrocyte-lineage OLIG1+ cells was reduced. OSM is specifically expressed by microglial cells and was strongly upregulated after injury. We observed microglial cells apposed to ependymal cells in vivo and co-cultures experiments showed that these cells upregulate OSMR in neurosphere cells. Collectively, these results support the notion that microglial cells and OSMR/OSM pathway regulate ependymal cells in injury. In addition, the generated high throughput data provides a unique molecular resource to study how ependymal cell react to spinal cord lesion.

cell biology↗