Biology subjects

Toth, Z.

Publications and source records attributed to Toth, Z..

16 recordsLinked to original sources

bioRxiv2025

Edge computer vision produces microarthropod-based high-throughput biodiversity metrics

Soil fauna is crucial for carbon cycling, controlling organic matter decomposition and contributing to ecosystem services1-7. Soil microarthropods are top-down regulators in the decomposer food web and serve as fundamental indicators of soil health. Yet, routine field-level monitoring remains restricted to resource-intensive research, leaving a critical gap in arable land management and policy. To address this, we developed Edapholog(R) extractor, a fully automated laboratory device that detects and identifies live soil microarthropods via real-time, AI-based image analysis, enabling taxonomic identification. Here, we demonstrate its accuracy across 319 arable fields spanning ten European countries. We show that computer vision can support ecological interpretation in arable systems and long-term studies on conservation tillage and cover cropping, offering a scalable tool for integrating soil biodiversity metrics into regenerative agriculture and carbon farming. We validated the system against classical taxonomy and found that across [~]35,000 microarthropod individuals, the device achieved an overall accuracy of 86%, sensitivity of 75%, and specificity of 99% compared to manual identifications. Community composition analyses revealed high similarities (83%), with minimal richness differences (7%) and low species replacement (13%) across countries, indicating that the AI does not introduce taxonomic bias. When applied in a long-term field experiment, the system detected significant taxon-specific responses to conservation tillage, with effect sizes ranging from 0.5 to 4. Total abundance, richness, and a soil biological health index were 39%, 47%, and 150% higher, respectively, under conservation tillage compared to conventional ploughing. These effects were statistically consistent between the automated and classical methods. However, while manual microscopy required several hours per sample, the AI-based system delivered immediate results without the need for taxonomic expertise. Edapholog(R) extractor offers exciting opportunities for rapid, scalable soil biodiversity monitoring for future sustainable land management.

ecology↗

bioRxiv2025

Can foraging in pesticide-treated patches become an ecological trap for pollinators? Modelling visitation patterns on a simulated landscape

Understanding the drivers of patch visitation in agricultural landscapes is essential for maintaining pollinator-mediated agroecosystem services, yet the extent to which behavioural mechanisms influence pollinators visitation rates has received little attention. Using an individual-based modelling framework (BEE-STEWARD), I examined how inadvertent social information (ISI) use and a recently documented pesticide-induced foraging bias influence nectar and pollen visitation rates of buff-tailed bumblebees (Bombus terrestris) to crop patches located near or far from the colonies. Simulations showed that ISI use primarily increased nectar visitation to all crop patches and pollen visitation to nearby crop patches, whereas foraging bias increased pollen visitation to all crop patches and nectar visitation to nearby crop patches. However, the two behavioural parameters had no interactive effects on crop visitation rates during nectar or pollen foraging. Despite the pronounced shifts in visitation patterns, total resource collection and colony demographics, including colony growth and reproductive output, remained largely unaffected. Overall, results indicate that ISI use and foraging biases are important drivers of spatial foraging patterns in bumblebees. Incorporating such behavioural pathways into pollinator foraging models may improve predictions of spatial visitation patterns and resource exploitation across agricultural landscapes, with potential implications for pesticide risk assessments.

ecology↗

bioRxiv2024

Long-read Transcriptomics of Caviid Gammaherpesvirus 1: Compiling a Comprehensive RNA Atlas

Caviid gammaherpesvirus 1 (CaGHV-1), formerly known as the guinea pig herpes-like virus, is an oncogenic gammaherpesvirus with a sequenced genome but an as-yet uncharacterized transcriptome. Using nanopore long-read RNA sequencing, we annotated the CaGHV-1 genome and constructed a detailed transcriptomic atlas. Our findings reveal diverse viral mRNAs and non-coding RNAs, along with mapped promoter elements for each viral gene. We demonstrated that the CaGHV-1 RTA lytic cycle transcription factor activates its own promoter, similar to KSHV, and that the CaGHV-1 ORF50 promoter responds to RTA proteins from other gammaherpesviruses, highlighting the evolutionary conservation of RTA-mediated transcriptional mechanisms. Additionally, our analysis uncovered extensive transcriptional overlap within the viral genome, suggesting a role in regulating global gene expression. Given its tumorigenic properties, broad host range, and non-human pathogenicity, this work establishes CaGHV-1 as a promising small animal model for investigating human gammaherpesvirus pathogenesis. IMPORTANCEThe molecular underpinnings of gammaherpesvirus pathogenesis remain poorly understood, partly due to limited animal models. This study provides the first comprehensive transcriptomic atlas of CaGHV-1, highlighting both coding and non-coding RNAs and revealing regulatory elements that drive viral gene expression. Functional studies of the CaGHV-1 RTA transcription factor demonstrated its ability to self-activate and cross-activate promoters from homologous gammaherpesviruses, reflecting conserved mechanisms of transcriptional control. These findings solidify CaGHV-1 as a unique and versatile small animal model, offering new opportunities to investigate gammaherpesvirus replication, transcriptional regulation, and tumorigenesis in a controlled experimental system.

genomics↗

bioRxiv2024

Unveiling the Origins and Genetic Makeup of the 'Forgotten People': A Study of the Sarmatian-Period Population in the Carpathian Basin

SO_SCPLOWUMMARYC_SCPLOWThe nomadic Sarmatians dominated the Pontic Steppe from 3rd century BCE and the Great Hungarian Plain from 50 CE until the Huns 4th-century expansion. In this study, we present the first large-scale genetic analysis of 156 genomes from 1st- to 5th-century Hungary and the Carpathian foothills. Our findings reveal minor East Asian ancestry in the Carpathian Basin (CB) Sarmatians, distinguishing them from other regional populations. Using F4-statistics, qpAdm, and IBD analysis, we show that CB Sarmatians descended from Steppe Sarmatians originating in the Ural and Kazakhstan regions, with Romanian Sarmatians serving as a genetic bridge between the two groups. We also identify two previously unknown migration waves during the Sarmatian era and a notable continuity of the Sarmatian population into the Hunnic period, despite a smaller influx of Asian-origin individuals. These results shed new light on Sarmatian migrations and the genetic history of a key population neighbouring the Roman Empire.

genetics↗

bioRxiv2023

KSHV 3.0: A State-of-the-Art Annotation of the Kaposi's Sarcoma-Associated Herpesvirus Transcriptome Using Cross-Platform Sequencing

Kaposis sarcoma-associated herpesvirus (KSHV) is a large, oncogenic DNA virus belonging to the gammaherpesvirus subfamily. KSHV has been extensively studied with various high-throughput RNA-sequencing approaches to map the transcription start and end sites, the splice junctions, and the translation initiation sites. Despite these efforts, the comprehensive annotation of the viral transcriptome remains incomplete. In the present study, we generated a long-read sequencing dataset of the lytic and latent KSHV transcriptome using native RNA and direct cDNA sequencing methods. This was supplemented with CAGE sequencing based on a short-read platform. We also utilized datasets from previous publications for our analysis. As a result of this combined approach, we have identified a number of novel viral transcripts and RNA isoforms and have either corroborated or improved the annotation of previously identified viral RNA molecules, thereby notably enhancing our comprehension of the transcriptomic architecture of the KSHV genome. We also evaluated the coding capability of transcripts previously thought to be non-coding, by integrating our data on the viral transcripts with translatomic information from other publications. IMPORTANCEDeciphering the viral transcriptome of KSHV is of great importance because we can gain insight into the molecular mechanism of viral replication and pathogenesis, which can help develop potential targets for antiviral interventions. Specifically, the identification of substantial transcriptional overlaps by this work suggests the existence of a genome-wide interference between transcriptional machineries. This finding indicates the presence of a novel regulatory layer, potentially controlling the expression of viral genes.

microbiology↗

bioRxiv2023

Novel Herpesvirus Transcripts with Putative Regulatory Roles in DNA Replication and Global Transcription

In the last couple of years, the rapid advances and decreasing costs of sequencing technologies have revolutionized transcriptomic research. Long-read sequencing (LRS) techniques are able to detect full-length RNA molecules in a single run without the need for additional assembly steps. LRS studies have revealed an unexpected transcriptomic complexity in a variety of organisms, including viruses. A number of transcripts with proven or putative regulatory role, mapping close to or overlapping the replication origins (Oris) and the nearby transcription activator genes, have been described in herpesviruses. In this study, we applied both newly generated and previously published LRS and short-read sequencing datasets to discover additional Ori-proximal transcripts in nine herpesviruses belonging to all of the three subfamilies (alpha, beta and gamma). We identified novel long non-coding RNAs (lncRNAs), as well as splice and length isoforms of mRNAs and lncRNAs. Furthermore, our analysis disclosed an intricate meshwork of transcriptional overlaps at the examined genomic regions. Our results suggest the existence of a super regulatory center, which controls both the replication and the global transcription through multilevel interactions between the molecular machineries.

molecular biology↗

bioRxiv2023

The Medicago truncatula nodule-specific cysteine-rich peptides, NCR343 and NCR-new35 are required for the maintenance of rhizobia in nitrogen-fixing nodules.

In the nodules of Inverted Repeat-Lacking Clade legumes, including M. truncatula, nitrogen-fixing rhizobia undergo terminal differentiation resulting in elongated and endoreduplicated bacteroids specialised for nitrogen fixation. This irreversible transition of rhizobia is mediated by host produced nodule-specific cysteine-rich (NCR) peptides, of which about 700 are encoded in the M. truncatula genome. Some of these NCR peptides, NCR169, NCR211 and NCR247, are essential for nitrogen-fixing symbiosis. The analysis of bacteroid and symbiotic host cell differentiation revealed that the symbiotic phenotype of M. truncatula mutants, Mtsym19, Mtsym20 and NF-FN9363, were defective likewise in the formerly studied ncr mutants, Mtdnf4-1 and Mtdnf7-2. The incomplete differentiation of bacteroids triggered premature senescence of rhizobia in the nitrogen fixation zones of mutant nodules. Mtsym19 and Mtsym20 mutants are defective in the same peptide NCR-new35 and the lack of NCR343 is responsible for the ineffective symbiosis of NF-FN9363. The activity of NCR-new35 is significantly lower and limited to the transition zone of the nodule compared with other crucial NCRs. The fluorescent protein-tagged version of NCR343 and NCR-new35 localize to the symbiotic compartment. Our discovery added two additional members to the group of NCR genes essential for nitrogen-fixing symbiosis in M. truncatula.

plant biology↗

bioRxiv2022

Synergistic interaction of caspofungin combined with posaconazole against FKS wild-type and mutant Candida auris planktonic cells and biofilms

The in vitro efficacy of caspofungin against FKS wild type and mutant Candida auris isolates was determined in the presence of posaconazole. Drug-drug interactions were assessed utilizing the fractional inhibitory concentration indices (FICIs), the Bliss independence model and a LIVE/DEAD viability assay. Median planktonic minimum inhibitory concentrations (pMICs) of C. auris isolates were between 0.5 and >2 mg/L for caspofungin and between 0.125 and >0.25mg/L for posaconazole. Median pMICs for caspofungin and posaconazole in combination showed a 4- to 256-fold decrease compared to caspofungin and a 2- to 512-fold decrease compared to posaconazole alone. The median sessile minimum inhibitory concentrations (sMICs) of isolates ranged from 32 to >32 mg/L and from 0.06 to >2 mg/L for caspofungin and posaconazole, respectively. Median sMICs for caspofungin and posaconazole in combination showed an 8- to 128-fold decrease compared to caspofungin and a 4- to 512-fold decrease compared to posaconazole alone. Caspofungin and posaconazole showed a synergistic interaction, especially against sessile cells (FICI from 0.033-0.375 and 0.091-0.5, and Bliss cumulative synergy volumes were 6.96 and 32.39 for echinocandin-susceptible and -resistant isolates, respectively). In line with the checkerboard-based findings, synergistic interactions were confirmed by a fluorescent microscopic LIVE/DEAD viability assay. The caspofungin-exposed (4 mg/L) C. auris biofilms exhibited increased cell death in the presence of posaconazole (0.03 mg/L) compared to untreated, caspofungin-exposed and posaconazole-treated sessile cells. The disrupted biofilm structure and increase in cell death was observed for both echinocandin-susceptible and echinocandin-resistant isolates. Despite the favourable effect of caspofungin in the presence of posaconazole, further in vivo studies are needed to confirm the clinical therapeutic potential of this combination when treating C. auris. Contribution to the fieldCandida auris is an emerging fungal pathogen, presumably related to global warming, which is associated with nosocomial infections and is considered a serious health threat worldwide. The treatment of C. auris infections is challenging due to the high level of drug resistance against the traditional antifungal agents. Given the low frequency of resistance to echinocandins, they are recommended as first-line therapy for the management of C. auris infections; however, treatment is complicated by the development of resistance in patients receiving long-term echinocandin treatment. In addition, the biofilm forming ability of this species further complicates the echinocandin-based therapeutic strategies. Combination-based approaches using existing drugs are viable alternatives to overcome the difficult-to-treat C. auris-related infections, including biofilm associated cases. In this study, we examined the in vitro efficacy of caspofungin and posaconazole against FKS wild-type and mutant C. auris planktonic cells and biofilms using classic checkerboard-based investigations and fluorescent imaging. Based on our results, the efficacy of caspofungin and posaconazole is unquestionable, having been confirmed against biofilms, especially in the case of FKS mutants at clinically achievable and safe drug concentrations. This study suggests that the administration of caspofungin with posaconazole may help to expand potential treatment strategies.

microbiology↗

bioRxiv2022

Physiological and transcriptional profiling of surfactin exerted antifungal effect against Candida albicans

Given the risk of Candida albicans overgrowth in the gut, novel complementary therapies should be developed to reduce fungal dominancy. This study highlights the antifungal characteristics of a Bacillus subtilis-derived secondary metabolite, surfactin with high potential against C. albicans. Surfactin inhibited the growth of C. albicans following a 1-hour exposure, in addition to reduced adhesion and morphogenesis. Specifically, surfactin did not affect the level of reactive oxygen species but increased the level of reduced glutathione. Surprisingly, ethanol production enhanced following 2 hours of surfactin exposure. Surfactin treatment caused a significant reduction in intracellular iron, manganese and zinc content compared to control cells, whereas the level of copper was not affected. Alongside these physiological properties, surfactin also enhanced fluconazole efficacy. To gain detailed insights into the surfactin-related effects on C. albicans, genome-wide gene transcription analysis was performed. Surfactin treatment resulted in 1390 differentially expressed genes according to total transcriptome sequencing (RNA-Seq). Of these, 773 and 617 genes with at least a 1.5-fold increase or decrease in transcription, respectively, were selected for detailed investigation. Several genes involved in morphogenesis or related to metabolism (e.g., glycolysis, fermentation, fatty acid biosynthesis) were down-regulated. Moreover, surfactin decreased the expression of ERG1, ERG3, ERG9, ERG10 and ERG11 involved in ergosterol synthesis, whereas genes associated with ribosome biogenesis and iron metabolism and drug transport-related genes were up-regulated. Our data demonstrate that surfactin significantly influences the physiology and gene transcription of C. albicans, and could contribute to the development of a novel innovative complementary therapy. ImportanceAlthough gut colonization by Candida albicans can be considered normal, it may be associated with intestinal diseases. Furthermore, Candida dominance in the gut may pose a potent risk for systemic candidiasis, especially for immunocompromised individuals. In recent years, interest has been growing for the use of Bacillus subtilis as a safe and effective probiotic for human healthcare. Surfactin is a B. subtilis-derived lipopeptide with potential antifungal activity; however, the mechanism underlying this remains unknown. In this study, surfactin negatively affected the adherence, morphogenesis and metabolism of C. albicans and increased ethanol production. These were associated with a reduction in intracellular iron, manganese and zinc while the copper content was not affected. Alongside these physiological modulations, surfactin also had a potent synergistic effect on fluconazole. Our results provide a definitive explanation for the surfactin-related antifungal effect of B. subtilis; furthermore, these data provide a good basis for future probiotic development.

microbiology↗

bioRxiv2022

Social information-mediated population dynamics in non-grouping prey

Inadvertent social information (ISI) use, i.e., the exploitation of social cues including the presence and behaviour of others, has been predicted to mediate population-level processes even in the absence of cohesive grouping. However, we know little about how such effects may arise when the prey population lacks social structure beyond the spatiotemporal autocorrelation originating from the random movement of individuals. In this study, we built an individual-based model where predator avoidance behaviour could spread among randomly moving prey through the network of nearby observers. We qualitatively assessed how ISI use may affect prey population size when cue detection was associated with different probabilities and fitness costs, and characterised the structural properties of the emerging detection networks that would provide pathways for information spread in prey. We found that ISI use was among the most influential model parameters affecting prey abundance and increased equilibrium population sizes in most examined scenarios. Moreover, it could substantially contribute to population survival under high predation pressure, but this effect strongly depended on the level of predator detection ability. When prey exploited social cues in the presence of high predation risk, the observed detection networks consisted of a large number of connected components with small sizes and small ego networks; this resulted in efficient information spread among connected individuals in the detection networks. Our study provides hypothetical mechanisms about how temporary local densities may allow information diffusion about predation threats among conspecifics and facilitate population stability and persistence in non-grouping animals. Significance StatementThe exploitation of inadvertently produced social cues may not only modify individual behaviour but also fundamentally influence population dynamics and species interactions. Using an individual-based model, we investigated how the detection and spread of adaptive antipredator behaviour may cascade to changes in the demographic performance of randomly moving (i.e., non-grouping) prey. We found that social information use contributed to population stability and persistence by reducing predation-related per capita mortality and raising equilibrium population sizes when predator detection ability reached a sufficient level. We also showed that temporary detection networks had structural properties that allowed efficient information spread among prey under high predation pressure. Our work represents a general modelling approach that could be adapted to specific predator-prey systems and scrutinize how temporary local densities allow dynamic information diffusion about predation threats and facilitate population stability in non-grouping animals.

animal behavior and cognition↗

bioRxiv2021

In vitro and in vivo interaction of caspofungin with isavuconazole against Candida auris planktonic cells and biofilms

The in vitro and in vivo efficacy of caspofungin was determined in combination with isavuconazole against Candida auris. Drug-drug interactions were assessed utilising the fractional inhibitory concentration indices (FICIs), the Bliss independence model and an immunocompromised mouse model. Median planktonic minimum inhibitory concentrations (pMICs) of 23 C. auris isolates were between 0.5 and 2 mg/L and between 0.015 and 4 mg/L for caspofungin and isavuconazole, respectively. Median pMICs for caspofungin and isavuconazole in combination showed 2-128-fold and 2-256-fold decreases, respectively. Caspofungin and isavuconazole showed synergism in 14 out of 23 planktonic isolates (FICI range 0.03-0.5; Bliss cumulative synergy volume range 0-4.83). Median sessile MICs (sMIC) of 14 biofilm-forming isolates were between 32 and >32 mg/L and between 0.5 and >2 mg/L for caspofungin and isavuconazole, respectively. Median sMICs for caspofungin and isavuconazole in combination showed 0-128-fold and 0-512-fold decreases, respectively. Caspofungin and isavuconazole showed synergistic interaction in 12 out of 14 sessile isolates (FICI range 0.023-0.5; Bliss cumulative synergy volume range 0.13-234.32). In line with the in vitro findings, synergistic interactions were confirmed by in vivo experiments. The fungal kidney burden decreases were more than 3 log volumes in mice treated with combination of 1 mg/kg caspofungin and 20 mg/kg isavuconazole daily; this difference was statistically significant compared with control mice (p<0.001). Despite the favourable effect of isavuconazole in combination with caspofungin, further studies are needed to confirm the therapeutic advantage of this combination when treating an infection caused by C. auris.

microbiology↗

bioRxiv2020

"The stressed bird in the hand": Influence of sampling design on the physiological stress response in a free-living songbird

Despite the widely used application of standardized capture-handling protocols to collect blood and assess the physiological stress response, the effect of the actual sampling design (e.g. timing and the number of blood samples) often differs between studies, and the potential implications for the measured physiological endpoints remain understudied. We, therefore, experimentally tested the effects of repeated handling and multiple blood sampling on the stress response in wintering free-living great tits (Parus major). We modified a well-established sampling protocol of avian studies by adding either an additional blood sample or a "sham-manipulation" (i.e. handling associated with the blood sampling procedure without venepuncture), to disentangle the effects of handling stress and blood loss. We combined three different stress metrics along the endocrine-immune interface to investigate the acute short-term stress response: total corticosterone levels (CORT), the heterophil/lymphocyte ratio (H:L), and the Leukocyte Coping Capacity (LCC). Our study provided three key results: i) no relationship between CORT-levels, LCC and H:L, confirming that these three parameters represent different physiological endpoints within the stress response; ii) contrasting dynamics in response to stress by the measured parameters and iii) no difference in stress levels 30 minutes after capture due to one additional blood sampling or handling event. By optimising the sampling design, our results provide implications for animal welfare and planning experimental procedures on stress physiology in passerine species. Summary StatementWhen testing the short-term stress response in free living passerines, both - the scientist and the bird may be better off with a 15-minute stress protocol.

physiology↗

bioRxiv2020

Insulin-like growth factor 1 induces oxidative damage, but does not affect survival in a songbird

Lifespan evolves as a compromise between antagonistic selection forces. Insulin-like growth factor 1 (IGF-1) is a pleiotropic hormone that regulates several life-history traits. High levels of IGF-1 have been linked to increased mortality, partly by causing oxidative stress. However, these effects have no experimental evidence in wild animals. We implanted microspheres loaded with exogenous IGF-1 into bearded reedlings, a common short-lived Eurasian songbird. The treatment elevated plasma IGF-1 levels for at least 24 h. Oxidative damage to lipids significantly increased the day after the manipulation in treated birds, but returned to baseline levels four days post-treatment. The treatment had no effect on survival over 16 months; however, birds with higher pre-treatment (baseline) IGF-1 levels had better survival prospects. These results suggest that, although high IGF-1 levels may induce oxidative damage, natural variation in this hormones level may reflect the outcome of individual optimization.

evolutionary biology↗

bioRxiv2019

Insulin-like growth factor 1 is related to the expression of plumage traits in a passerine species

Avian plumage colors and ornaments are ideal models to study the endocrine mechanisms linking sexually selected traits and individual parameters of quality and condition. The insulin-like growth factor 1 (IGF-1), an evolutionarily highly conserved peptide hormone, represents a link between body condition and the individual capacity to grow elaborated ornamental features, due to its regulatory role in cell proliferation and differentiation and its high sensitivity to the nutritional state of individuals. We investigated whether IGF-1 levels during molting affect the expression of multiple ornaments in a sexually dichromatic passerine species, the bearded reedling (Panurus biarmicus). We collected blood samples of males and females shortly before the molting completed and measured the size and colors of ornamental traits. Our results indicate that in males, structural plumage colors, the size of the melanin based ornament (beard) and tail length are independent traits. IGF-1 levels predict the length of the tail and the expression of male structural plumage components (UV-coloration), but not the melanin based ornament. In females plumage color and tail length were independent traits, which were not related to IGF-1 levels. Overall, our results indicate for the first time that IGF-1 could play a role in the development of secondary sexual characters in a passerine species.

evolutionary biology↗

bioRxiv2018

Exploring the mechanistic link between corticosterone and insulin-like growth factor-1 in a wild passerine bird

BackgroundPhysiological regulators of life history trade-offs need to be responsive to sudden changes of resource availability. When homeostasis is challenged by unpredictable stressors, vertebrates respond through a set of physiological reactions, which can promote organismal survival. Glucocorticoids have been traditionally recognized as one of the main regulators of the physiological stress response, but the role of an evolutionarily more conserved pathway, the hypothalamic-pituitary-somatotropic (HPS) axis producing insulin-like growth factor-1 (IGF-1) has received much less attention. Although IGF-1 is known to affect several life history traits, little is known about its role in the physiological stress response and it has never been studied directly in adult wild animals.\n\nMethodsIn this study, we combined field observations with a controlled experiment to investigate how circulating levels of IGF-1 change in response to stress and whether this change is due to concomitant change in glucocorticoids in a free-living songbird, the bearded reedling Panurus biarmicus. We used a standard capture-restraint protocol in field observation, in which we took first and second (stress induced: 15 minutes later) samples. In a follow-up experiment, we used a minimally invasive oral corticosterone manipulation.\n\nResultsWe showed that corticosterone levels significantly increased while IGF-1 levels significantly decreased during capture and handling stress. However, change in corticosterone levels were not related to change in IGF-1 levels. We found that experimentally elevated corticosterone levels did not affect IGF-1 levels.\n\nDiscussionOur results are the first to highlight that circulating IGF-1 levels are responsive to stress independently from glucocorticoids and suggest that the HPS axis is an autonomous physiological pathway that may play an important role as regulator of life-history decisions.

physiology↗

bioRxiv2018

Systemically administered MSCs given 24hrs after osteotomy do not affect bone formation in rat distraction osteogenesis

Distraction osteogenesis is a unique postnatal bone formation employed by orthopaedic surgeons to treat many conditions, however, the overall time to external frame removal can be extensive. Any strategies that accelerate healing would improve patient care. Distraction osteogenesis research in the past decade has shown that direct stem cell implantation enhances new bone formation. Systemic implantation would be more clinically desirable. Systemically delivered stem cells have been shown to home to a mandibular distraction site; however, effects on bone formation have not been studied. Ten-week-old, male Sprague-Dawley rats underwent surgery to implant an external fixator-distractor and an osteotomy was performed. Twenty-four hours postoperatively, each rat received tail vein injections of either saline or 10^6 fluorescently labeled primary mesenchymal stem cells. Animals in the validation groups were euthanized two days after surgery and the femora processed for histology. Animals in the experimental groups were given five days of latency, then the femur was lengthened once daily for five days (0.75mm/day, 3.75mm total). Following four weeks of consolidation, the animals were euthanized and the femora were evaluated by microCT and histology to quantify new bone formation. Labeled stem cells were found at the distraction site in validation animals. However, there were no differences in any bone or soft tissue outcomes. Systemic stem cell administration 24 hours after surgery does not improve DO outcomes. It is possible that the animal model was not challenging enough to discriminate any augmentation provided by stem cells.

bioengineering↗