Biology subjects

Fusellier, M.

Publications and source records attributed to Fusellier, M..

4 recordsLinked to original sources

bioRxiv2025

Brain size reduction in dogs was already established at least by the Late Neolithic of western Europe, 5,000 years ago

The timing and causes of brain size reduction in domestic dogs remain uncertain. Using endocasts volume as a proxy for brain size, this study provides a first insight into long-term brain size evolution in the wolf-dog lineage. We compared endocranial volumes of 185 modern and 22 prehistoric wolves and dogs ranging from Western Europe to Australia, and spanning the Pleniglacial (35 Ky BP) to the Late Neolithic (5 Ky BP). Our results reveal that Pleistocene so called "protodogs" show no brain size reduction compared to coeval Pleistocene wolves. Instead, we observed a slightly larger relative endocranial volume in the 35,000-year-old protodog from Goyet, which could suggest increased behavioural flexibility in the presence of humans. This hypothesis needs to be tested further. In contrast, Late Neolithic dogs show a drastic 46% brain size reduction with an endocranial volumes comparable to modern small terrier and toy breeds. The anxious and wary temperaments of these Late Neolithic dogs, induced by the brain tissue reorganization associated with such a size reduction, could have served an alerting purpose, among the many other potential roles dogs could have played within this Late Neolithic socio-ecosystems.

zoology↗

bioRxiv2025

A degradable nanofibrous scaffold of poly(ε-Caprolactone-co-Lactide) for annulus fibrosus repair

The intervertebral disc (IVD) is a key contributor to the spines biomechanical functions. It consists of a gelatinous core (nucleus pulposus, NP) surrounded by a fibrous ring (annulus fibrosus, AF). Accumulation of microcracks and tears in the AF can lead to NP herniation outside the disc space, compressing the nerve roots and causing pain. Herniation is a leading cause of low back pain and represents a major socioeconomic burden, with no effective regenerative treatment currently available. Previously, we demonstrated the potential of a poly({varepsilon}-caprolactone) (PCL)-based implant for the closure of an annulus fibrosus (AF) defect. However, the slow in vivo degradation of PCL may hinder timely AF regeneration. Here, we hypothesized that accelerating PCL degradation kinetics by incorporating a lactide component, known for its rapid degradation, could enhance AF repair. To that aim, PCLA polymers of {varepsilon}-caprolactone and lactide were synthesised as a copolymer (C-CL90%LA10%) or a blend (B-PCL80%PLA20%). These polymers were electrospun into aligned nanofibrous sheets, which were then assembled into a biomimetic multi-lamellar 3D implant. Cytocompatibility was assessed in vitro using ovine AF cells and ex vivo using a bovine tail disc model. In vitro, PCLA sheets promoted ovine AF cell alignment, proliferation, and expression of type I and II collagen. Ex vivo, the multi-lamellar implant remained in place within a full-thickness (4 mm) annular defect in bovine tail discs for 4 weeks, with initial cell infiltration. Degradation and regenerative potential were then evaluated in an ovine lumbar full-thickness annular defect model at 1 month (n=4) and 6 months (n=10) after implantation. Histological and immunohistochemical analyses revealed substantial cellular infiltration and neo-tissue ingrowth within implant layers, despite implant displacement in some cases. At 1 month, all implants retained their multi-lamellar structure with no visible degradation. By 6 months, the copolymer implants exhibited marked degradation, whereas PCL and blend implants remained structurally intact. Furthermore, ex vivo biomechanical testing revealed comparable flexibility to intact but much lower than non-implanted controls in axial rotation. This study confirms the accelerated degradation kinetics of PCLA copolymers within the disc microenvironment and demonstrates that the multi-lamellar PCLA implant can guide AF tissue repair. Further optimization is needed to enhance implant retention and ensure long-term functional integration.

bioengineering↗

bioRxiv2025

Transcriptomic and functional comparison of cells isolated from healthy and degenerated ovine intervertebral discs

Structured abstractO_ST_ABSBackgroundC_ST_ABSIntervertebral disc degeneration (IVDD) is a leading cause of chronic low back pain and disability. Understanding the cellular and molecular mechanisms underlying disc degeneration is crucial for developing effective therapies. Sheep have emerged as a promising large-animal model for IVDD research due to their similarities with humans. They exhibit resembling spine anatomy and biomechanics, and they develop spontaneous age-associated degeneration of the disc. However, the specific cellular alterations occurring in annulus fibrosus (AF) and nucleus pulposus (NP) ovine cells during degeneration remain poorly characterized. In vitro, the benefits of using cells from aged sheep over young ones to mimic degenerative processes remain to be tested. MethodsAF and NP cells from young and aged sheep were analysed using bulk RNA sequencing, with a focus on two hallmarks of IVDD: cellular senescence and metabolic alterations. Functional assays completed this focus by assessing cells response under basal conditions and after pro-degenerative stimuli (IL-1{beta}, senescence induction). In addition, bulk transcriptomic data were deconvoluted using a reference single-cell RNA-seq dataset from healthy and degenerated human discs, and gene co-expression modules were compared across species. ResultsMRI and histological analyses revealed homogeneous mild degeneration across all lumbar discs in aged sheep, while lamb discs were uniformly healthy. Cells transcriptomic profiling identified robust age- and tissue-specific signatures, with aged NP and AF cells showing upregulation of inflammatory mediators, ECM-remodelling enzymes, and senescence-associated pathways. Cross-species analysis revealed shared transcriptional modules between aged sheep cells and human degenerated disc cells, supporting the translational relevance of the ovine model. Remarkably, young and aged cells shared a similar functional behaviour when exposed to stress-related stimuli. ConclusionsThis work confirms the compatibility of sheep cells with in vitro testing and their relevance to model human IVDD. Cross-validation with human single-cell data further highlights common pathogenic pathways, reinforcing the translational potential of the model. However, no added benefits were found in using older animals compared to younger ones as cell sources in functional assays. HighlightsO_LITranscriptomic profiling of AF and NP cells from young and aged sheep C_LIO_LIAged cells show inflammatory, ECM-remodelling and senescence signatures C_LIO_LIDeconvolution with human scRNA-seq links aged ovine and degenerated discs C_LIO_LISheep cells retain in vitro responsiveness to pro-degenerative stimuli C_LIO_LISupports the ovine model as a translational tool for IVDD research C_LI

cell biology↗

bioRxiv2025

BIOFABRICATION OF AN OVINE INTERVERTEBRAL DISC MODEL BY COMBINING A POLYCAPROLACTONE FRAME WITH A BIOPRINTED ALGINATE HYDROGEL

The intervertebral disc (IVD) primarily comprises an outer ring of collagen fibers (annulus fibrosus, AF), which encases a soft, gelatinous core (nucleus pulposus, NP). Existing in vitro models have failed to integrate these two tissues effectively or accurately replicate their intricate organization. By combining two biofabrication techniques, we developed a novel 3D in vitro model that closely mimics the organization of an ovine IVD. Our approach employs a polycaprolactone (PCL) frame produced via melt electrowriting to recreate the multilamellar architecture of the annulus fibrosus. Ovine primary cells, encapsulated in a photocrosslinkable alginate hydrogel, were precisely extruded within the multilamellar structure, thereby mimicking the native shape and size of an ovine disc. The bioink containing the NP cells was deposited at the center of the construct, while the bioink with the AF cells was strategically layered in between the lamellae of the PCL frame. Photocrosslinking was optimized to match the native stiffness of the disc. The constructs were maintained in culture for 28 days, during which we thoroughly assessed reproducibility, stability, and cell viability and phenotype. The results unequivocally demonstrated that the PCL frame effectively guided the alignment and proliferation of AF cells, while the alginate hydrogel preserved NP cell phenotype. This model successfully replicates the organization of the IVD, providing a promising platform for advancing our understanding of disc biology and driving the development of novel therapeutic strategies.

bioengineering↗