Biology subjects

Roell, D.

Publications and source records attributed to Roell, D..

4 recordsLinked to original sources

bioRxiv2026

Age-Dependent Fibroblast Programs Govern Regenerative and Fibrotic Tendon Repair

Tendon injuries often result in fibrosis, compromising function and predisposing to re-injury. Here, we used a full-width, non-repair Achilles tendon transection model in young (3 weeks old) and adult (18-20 weeks) rats to elucidate the cellular mechanisms governing regenerative versus fibrotic healing. Functional and biomechanical analyses revealed that young tendons recovered motion and load-bearing capacity more rapidly but exhibited more fibrotic early healing. Single-nuclei RNA sequencing identified seven major cell populations within the connective tissue compartment. Adult tendons maintained a "synthetic fibroblast" population marked by upregulated ECM synthesis, reduced stress-related gene expression, whereas young tendons favored expansion of Cxcl12/Lrp6/Gas6 fibrotic fibroblasts linked to oxidative and pro-angiogenic signaling. The young group showed sustained activation of Nox4-Gas6 pathways driving a self-reinforcing fibrotic circuit. These findings define a fibroblast lineage bifurcation that dictates oxidative stress signaling as a key regulator of fibrotic remodeling, highlighting potential therapeutic targets to promote regenerative tendon repair.

developmental biology↗

bioRxiv2026

Modulating Inflammation in Post-Traumatic Osteoarthritis using iPSC-derived Anti-inflammatory Macrophages

Post-traumatic osteoarthritis (PTOA) is a common long-term consequence of joint injury and a major cause of chronic pain and disability, yet no disease-modifying therapies are currently available. A central barrier to effective intervention is the persistence of maladaptive synovial inflammation, driven in part by macrophage-mediated signaling that sustains tissue degeneration and pain. Here, we developed a scalable, chemically defined platform to generate human induced pluripotent stem cell (iPSC)-derived anti-inflammatory macrophages (iMac-M2) as an off-the-shelf cell therapy designed to restore joint immune homeostasis after injury. These cells maintained a stable anti-inflammatory phenotype and function under osteoarthritis-relevant inflammatory conditions and suppressed inflammatory and catabolic responses in human joint cell co-culture systems. In a preclinical model of PTOA, intra-articular delivery of iMac-M2 after injury improved functional and structural outcomes while modulating synovial inflammatory and pain-associated transcriptional programs. Treatment was well tolerated, with no evidence of systemic immune activation or ectopic tissue formation. Together, these findings support iPSC-derived macrophage therapy as a clinically translatable immunomodulatory strategy to interrupt early inflammatory drivers of PTOA and preserve joint health following injury.

cell biology↗

bioRxiv2024

How to measure functional connectivity using resting-state fMRI? A comprehensive empirical exploration of different connectivity metrics

BackgroundFunctional connectivity in the context of functional magnetic resonance imaging is typically quantified by Pearso[n]s or partial correlation between regional time series of the blood oxygenation level dependent signal. However, a recent interdisciplinary methodological work proposes more than 230 different metrics to measure similarity between different types of time series. ObjectiveHence, we systematically evaluated how the results of typical research approaches in functional neuroimaging vary depending on the functional connectivity metric of choice. We further explored which metrics most accurately detect neural decline induced by age and malignant brain tumors, aiming to initiate a debate on how best assessing brain connectivity in functional neuroimaging research. MethodsWe addressed both research questions using four independent neuroimaging datasets, comprising multimodal data from a total of 1187 individuals. We analyzed resting-state functional sequences to calculate functional connectivity using 20 representative metrics from four distinct mathematical domains. We further used T1- and T2-weighted images to compute regional brain volumes, diffusion-weighted imaging data to build structural connectomes, and pseudo-continuous arterial spin labeling to measure regional brain perfusion. ResultsFirst, our results demonstrate that the results of typical functional neuroimaging approaches differ fundamentally depending on the functional connectivity metric of choice. Second, we show that correlational and distance metrics are most appropriate to cover neural decline induced by age. In this context, partial correlation performs worse than other correlational metrics. Third, our findings suggest that the FC metric of choice depends on the utilized scanning parameters, the regions of interest, and the individual investigated. Lastly, beyond the major objective of this study, we provide evidence in favor of brain perfusion measured via pseudo-continuous arterial spin labeling as a robust neural entity mirroring age-related neural and cognitive decline. ConclusionOur empirical evaluation supports a recent theoretical functional connectivity framework. Future functional imaging studies need to comprehensively define the study-specific theoretical property of interest, the methodological property to assess the theoretical property, and the confounding property that may bias the conclusions.

neuroscience↗

bioRxiv2018

Use of IFNγ/IL10 ratio for stratification of hydrocortisone therapy in patients with septic shock

BackgroundLarge clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may however benefit depending on their individual immune response.\n\nMethodsWe performed an exploratory analysis of the CORTICUS trial database employing machine learning to a panel of 137 variables collected from 83 patients (60 survivors, 23 non-survivors) including demographic and clinical measures, organ failure scores, leukocyte counts and circulating cytokine levels. The identified biomarker was validated against data collected from patients enrolled into a cohort of the Hellenic Sepsis Study Group (HSSG) (n=162) and two data sets of two other clinical trials. Ex vivo studies were performed on this biomarker to assess a possible mechanistic role.\n\nResultsA low serum IFN{gamma}/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this ratio for a decision rule, we found significant improvement in survival in the groups of patients being in compliance with the prediction rule (discovery set: OR=3.03 [95% Cl: 1.05-8.75], P=0.031, validation set: OR=2.01 [95% CI: 1.04-3.88], P=0.026). Applying the rule to two further, smaller datasets showed the same tendency. Mechanistic studies revealed that IFN{gamma}/IL10 was negatively associated with pathogen load in spiked human blood. An in silico analysis of published IFN{gamma} and IL10 values in bacteremic and non-bacteremic SIRS patients supported this association between the ratio and pathogen burden.\n\nConclusionIf confirmed prospectively, the IFN{gamma}/IL10 ratio could be used as a rapidly available theranostic for use of hydrocortisone therapy in septic shock.

immunology↗