Comparative analysis of the radiobiological effects of laser-driven VHEE vs. conventional electrons using in vitro, ex vivo, and in vivo models

Giaccaglia, C.; Bayart, E.; Dubail, M.; Varma, C.; Heinrich, S.; Gautier, J.; Tafzi, A.; Kononenko, L.; Goddet, J.-p.; Lamarre-Jouenne, I.; Fouillade, C.; Flacco, A.

doi:10.1101/2025.05.27.656200

bioRxiv · 10.1101/2025.05.27.656200

Comparative analysis of the radiobiological effects of laser-driven VHEE vs. conventional electrons using in vitro, ex vivo, and in vivo models

Giaccaglia, C.·Bayart, E.·Dubail, M.·Varma, C.·Heinrich, S.·Gautier, J.·Tafzi, A.·Kononenko, L.·Goddet, J.-p.·Lamarre-Jouenne, I.·Fouillade, C.·Flacco, A.

View original source ↗Export metadata ↓

Abstract

PurposeThis study systematically investigates the radiobiological effects of Very High Energy Electrons (VHEE) generated by a laser-plasma accelerator (LPA), in comparison with Conventional Intermediate Energy Electrons (CIEE) from a conventional linear accelerator (LINAC). Using in vitro, ex vivo, and in vivo models, we evaluate and compare their potential toxicity on healthy tissues. Methods and MaterialsCell survival, tissue response, and developmental toxicity were assessed across three biological models. In vitro, human fibroblasts (MRC5-hTERT) were used to generate post-irradiation survival curves. Ex vivo, precision-cut lung slices (PCLS) from mice were analyzed for radiation-induced inhibition of cell proliferation. In vivo, zebrafish embryos were used to evaluate developmental toxicity through body length and spinal curvature measurements. VHEE irradiations were performed using a broadband electron beam spanning 50-300 MeV, using the Salle Jaune LPA (Laboratoire dOptique Appliquee, France), while CIEE exposures were performed with a 7 MeV conventional LINAC (Institut Curie, France). ResultsIn vitro, MRC5-hTERT cells showed no significant difference in radiosensitivity between VHEE and CIEE, with comparable D10 values (p-value = 0.7). In the ex vivo model, both beams induced a dose-dependent decrease in cell division with no significant inter-beam differences at any dose level (p-value > 0.99). In vivo, zebrafish embryos exhibited dose-dependent body shortening and increased spinal curvature following both VHEE and CIEE exposure. No significant differences were observed between the two modalities at matched doses for any measured metric (p-value[≥] 0.5). ConclusionThis study presents the first comprehensive radiobiological evaluation of a laser-driven VHEE beam across multiple biological models. Under the investigated conditions, VHEE and CIEE irradiations exhibit similar biological toxicity. These findings support the feasibility and potential of VHEE generated with LPA for future clinical applications.

Source connections

Published article ↗

Explore related subjects

cell biology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Giaccaglia, C., Bayart, E., Dubail, M., Varma, C., Heinrich, S., Gautier, J., Tafzi, A., Kononenko, L., Goddet, J.-p., Lamarre-Jouenne, I., Fouillade, C., Flacco, A.. 2025-05-28. Comparative analysis of the radiobiological effects of laser-driven VHEE vs. conventional electrons using in vitro, ex vivo, and in vivo models. https://doi.org/10.1101/2025.05.27.656200

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Sequence context and partner availability specify divergent cell fates from a single transcription factor

Transcription factors drive the gene regulatory networks that control developmental transitions, yet which of their many targets a cell uses remains unresolved. Expressing Cebp, Cebp{beta} or Cebp{delta} identically, alone or with Oct4, Sox2, Klf4 and cMyc, gave four outcomes: adipocyte from fibroblasts and neural stem cells, trophectoderm from embryonic stem cells, and myeloid from B cells. Raising Cebp levels changed how many sites it reached, not which sequence it read: clustered motifs maintained somatic enhancers, while spillover onto low-copy sites created de novo enhancers carrying composites of Cebp and cell-type-restricted partners. In fibroblasts, Cebp also redistributed Oct4, Sox2 and Klf4 from early targets, blocking iPSC formation. Supplying the predicted partners rewrote the output: Spi1 redirected Cebp into parallel adipogenic and myeloid programs, via a transient PpargCD45 state using separate enhancers for each; TFAP2C abolished adipogenic conversion. Motif density and partner composites therefore assemble a factor's instructive output in the receiving cell.

cell biology↗

bioRxiv2026

High-content screening identifies FDA-approved activators of mitophagy

Mitochondrial diseases are highly heterogeneous disorders caused by defects in oxidative phosphorylation, for which only limited therapeutic options are available. The elimination of dysfunctional mitochondria via mitophagy activation is an attractive strategy to treat several mitochondrial diseases, irrespective of the underlying genetic defect. To identify pharmacological activators of this pathway, we performed a high-content screening of 1,971 FDA-approved compounds using cellular reporters of TFEB nuclear translocation and mitophagy. This screening identified 294 compounds that promoted TFEB translocation, nine of which increased the number of mitolysosomes without compromising cell viability or damaging mitochondria. Among the selected compounds, Meptazinol and Ponatinib emerged as the top-ranked mitophagy inducers in fibroblasts from patients with complex I and IV deficiency, respectively, and were prioritised for further characterisation. However, they did not rescue the bioenergetic defect, suggesting that the stimulation of mitophagy per se is not sufficient to ameliorate the OXPHOS defect in mitochondrial diseases. Overall, our findings establish a scalable platform for the identification of pharmacological activators of TFEB and identify candidate compounds for therapeutic modulation of mitophagy.

cell biology↗

bioRxiv2026

Matrix Gla Protein deficiency reveals a previously unrecognized mucosal calcification in the mouse airways

Tracheal calcification is a common finding that is considered to have limited clinical significance when detected most often in elderly individuals. Despite its frequent occurrence, the cellular and molecular mechanisms at the origin of tracheal calcification remain largely unexplored. In this context, we aimed to characterize the development of tracheal calcification, and to determine the role of matrix Gla protein (MGP), a major inhibitor of ectopic calcification whose genetic or pharmacologic deficiency is associated with premature tracheal calcification in humans. We found that wild-type mice undergo an unexpected early physiologic calcification of the tracheal cartilage rings beginning around one month after birth. This calcification progresses in a dynamic rostro-caudal sequence through a process involving terminal differentiation of tracheal chondrocytes. These findings challenge the prevailing view that tracheal cartilage is a permanent hyaline cartilage and instead reveals an early and highly organized physiologic calcification process. Furthermore, our findings further identify MGP as a key regulator of calcification within the respiratory tract. Indeed, MGP deficiency not only markedly accelerates tracheal cartilage calcification through a similar pattern and mechanism but also induces a previously unrecognized calcification of the tracheal mucosa, a lesion absent in wild-type mice. These alterations could partly explain the respiratory manifestations observed in MGP-deficient patients having Keutel syndrome, which include dyspnea, cough, stridor, and recurrent infections, symptoms previously being mainly attributed to calcification of the tracheal cartilage rings.

cell biology↗