Biology subjects

Kochan, M.

Publications and source records attributed to Kochan, M..

3 recordsLinked to original sources

bioRxiv2026

Multi-Lab Testing of Early Preclinical Discoveries Identifies Promising Treatments

A fundamental challenge in drug development is the frequent failure of early laboratory research to translate into clinical benefit. One promising solution is to confirm findings from exploratory single-laboratory studies across multiple laboratories before clinical testing. We investigated this approach following the conduct of preclinical multi-laboratory studies across different fields of medicine. For this, we evaluated effect sizes, experimental rigor, and a set of criteria to identify determinants of confirmation success. When tested under increased rigor, only a fraction of multi-laboratory studies confirmed the initial results. The underlying effect size reduction was associated with outcome-relevant experimental differences between exploratory and confirmatory stages. In summary, multi-laboratory studies proved highly informative and served as an effective filter for promising treatments.

scientific communication and education↗

bioRxiv2026

A novel application tunnel in combination with medical training reduces stress induced by frequent intraperitoneal injections and blood sampling in mice

Handling-induced stress represents a major burden on laboratory mice and is heavily influenced by the handling technique. As such, tail-handling induces much higher stress than cup- or tunnel-handling, which is further aggravated by interventions, e.g. injections, which require even harsher fixation methods. Previous studies demonstrated that habituation protocols can improve animal welfare during handling and interventions. Here, we developed a medical training program and an alternative fixation method using an application tunnel in the context of a liver cancer model, where frequent intraperitoneal injections over many weeks are needed to induce tumor development. The training regimen consisted of 5 sessions over 2 weeks, which gradually introduced the animals to being touched by handlers and restrained for procedures. The training program was completed once before the start of any interventions, additional training sessions were performed biweekly during the entire course of the experiments. The animals were randomized to receive injections either in the novel application tunnel or using conventional fixation. Training effect was continuously monitored by measuring the latency to interact with the experimenter, the surface body temperature and by movement tracking. The latency to interact rapidly decreased during initial training sessions, and this effect was sustained throughout the course of treatment. Movement tracking demonstrated that mice injected inside the tunnel were more active and returned to their normal behavior after injections faster than conventionally restrained mice. Those mice also showed less signs of defecation and urination. Furthermore, the tunnel had a positive influence on the well-being of mice during blood sampling demonstrated by reduced signs of pain and faster willingness to interact with the handler after the procedure. In conclusion, habituation of the mice to the interventions with medical training and the improved handling procedure during ip injections and blood draws durably reduces stress levels and improves welfare of mice.

immunology↗

bioRxiv2025

The cortical microenvironment drives early immune organization and controls early osteoclastogenesis in bone healing

Bone regeneration is a complex, tightly-regulated process involving coordinated interactions of immune and stromal cells. Early phases of healing rely on the timely clearance of debris, a task primarily carried out by macrophages and osteoclasts. However, the sequence of events leading to the presence of osteoclasts at the fracture site and how this is shaped by local tissue microenvironments remains poorly understood, particularly at single-cell and spatial resolution. Using single-cell RNA sequencing and multi-epitope ligand cartography, we mapped the spatial organization of distinct cell compartments engaged in early fracture healing in both young and aged mice at the start of healing. Surprisingly, we found that young mice exhibited an increased presence of activated osteoclasts at day 7, concentrated within the cortical niche. This compartment was also characterized by a spatially restricted immune response with a selective accumulation of distinct macrophage types jointly interacting with neutrophils and stromal cells. This raised the possibility that local cell organization influences osteoclast precursor differentiation. We identified a distinct Spp1hi macrophage subset restricted to the cortex, which acted as a transitional precursor population giving rise to osteoclasts. Neutrophils preceded this Spp1hi macrophage accumulation and may promote their recruitment through chemotactic signaling. This coordination was less pronounced in aged mice despite preserved transcriptional states. In parallel, stromal cells in young animals displayed higher expression of essential niche factors further supporting local osteoclastogenesis at the cortex. Together, our findings identify distinct macrophage precursors and reveal early, cortex-specific niche activity supporting osteoclastogenesis. This provides a new framework for understanding the initiation of spatial immune-stromal interactions for the early stages of regeneration.

immunology↗