A porcine model of postoperative intra-abdominal adhesion formation was established using Yucatan mini pigs. The protocol combines midline laparotomy, small bowel resection with two-layer primary anastomosis, and a unilateral, parietal peritoneal abrasion in the format of an open abdominal surgical procedure. Adhesion formation was assessed four weeks postoperatively using established gross and histologic scoring criteria, with evaluations performed by blinded observers. Adhesions developed in all animals using this model and were multifocal, involving bowel loops, between the bowel and abdominal wall, involving the peritoneum overlying other organs in the abdomen (e.g. the liver), and operative sites, with variable severity. Histological analysis at four weeks demonstrated adhesions composed predominantly of extracellular matrix, fibroblasts, and blood vessels, consistent with a remodeling-phase wound healing tissue phenotype. This model is relevant for the study of abdominal adhesion fibrosis biology and/or the translational evaluation of candidate anti-adhesion therapeutics. By integrating a clinically relevant intestinal surgical procedure with a defined peritoneal injury and a standardized assessment strategy, this protocol provides a reproducible approach for inducing and evaluating postoperative intra-abdominal adhesions in a large animal model.

Abstract Germline mutations in CDH1 are associated with early-onset diffuse gastric adenocarcinoma. There is no gold standard for screening and management, and endoscopic surveillance is often insufficient for detecting early disease. Prophylactic gastrectomy is maximally preventive but is a major operation associated with significant morbidity and extensive lifestyle modifications. Therefore, there is a need to better understand the pathophysiological features underlying carcinogenesis in the setting of CDH1 mutation. To address this gap, we performed spatial transcriptomic profiling on 29 formalin-fixed paraffin-embedded sections from 8 patients with various stages of gastric adenocarcinoma, including one patient with a germline CDH1 mutation (c.1936+5G>A) found to have multifocal intramucosal poorly cohesive signet-ring cell carcinoma. Image-based cell segmentation and subcellular transcript detection enabled identification of diverse epithelial cell types, as well as their stromal and immune neighborhoods. Epithelial cells from the specimen harboring the germline CDH1 mutation expressed lower levels of CDH1 compared with other samples. Although morphologically normal-appearing, mucosal layers in these sections exhibited altered transcriptomic profiles characterized by an expanded epithelial population with high MUC1 expression. MUC1 is a transmembrane glycoprotein frequently upregulated in various cancers, with a cytoplasmic domain capable of interacting with several intracellular signaling partners, particularly β-catenin. Gene regulatory network analysis revealed a gradient of CTNNB1/β-catenin activation program, suggesting a potential interplay between CDH1 loss-of-function, MUC1 overexpression, and β-catenin pathway dysregulation. These findings reveal a novel MUC1-overexpressing epithelial population associated with CDH1 mutation and early-onset gastric adenocarcinoma, providing new rationales for developing surveillance biomarkers and targeted therapies. Citation Format: Chuner Guo, Rosyli F. Reveron-Thornton, Xiaomo Li, James P. Agolia, Maria Moozhiyil Korah, Peter Yuxin Xie, Amanda Gonçalves, Angela Tabora, Lily Xia, Natali Barakat, George Poultsides, Byrne Lee, Amanda R. Kirane, Deshka Foster, Michael T. Longaker, Gregory W. Charville, Daniel Delitto. A MUC1-overexpressing epithelial population is associated with CDH1 loss-of-function gastric adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2270.

Here, we present a protocol to interrogate the role of creeping fat (CF) and mechanical tension in Crohn's disease (CD) using a surgical mouse model of intestinal fibrosis. We describe steps for preoperative preparation, microsurgical techniques for stricture formation and mechanical stretching, and model variations such as mesenteric grafts. We then detail procedures for postoperative harvest, tissue embedding, and sectioning procedures. This model induces localized CF formation and transmural fibrosis, features distinct from those observed in chemical colitis models. For complete details on the use and execution of this protocol, please refer to Bauer-Rowe et al.1

BACKGROUND:Critical-sized bone defects resulting from tumors, trauma, or surgery present a significant clinical challenge due to its poor self-regenerating capabilities and limited therapeutic options. Mesenchymal stem cells (MSCs) have shown promise in bone regeneration, possibly mediated through their secretion of bioactive factors rather than direct engraftment and differentiation. MSC-derived extracellular vesicles (EVs) deliver micro-RNAs (miRs), proteins, and lipids that may modulate bone regeneration. METHODS:EVs were isolated by differential ultracentrifugation from osteogenically induced human adipose-derived stem cells (hASCs), treated with or without the small molecule SB431542, an inhibitor of TGFβ signaling (EV-hASCs[-/+]SB). EVs were characterized using western blot and nanoparticle tracking analysis. hASCs were cultured with EV-hASCs[-/+]SBs to assess bone regeneration in vitro. Bone regeneration was assessed in vivo in calvarial defects treated with (EV-hASCs[-/+]SB). EV "cargo" was analyzed for miR-content. RESULTS:Enhanced osteogenesis is shown in vitro and in vivo upon treatment with EV-hASCs[+]SB. EV-hASCs[+]SB-enriched-miR-20a-5p was identified as a modulating factor in osteogenesis, silencing BAMBI and enhancing early downstream phosphorylation of SMAD1/5 and late activation of β-catenin in hASCs undergoing osteogenic differentiation, targets of bone morphogenetic protein (BMP) and canonical Wnt (cWnt) signaling pathways. CONCLUSION:EVs act as carriers for miR-mediated pro-osteogenic signaling, harnessing the therapeutic potential of MSCs in the context of bone tissue repair.

Abstract Given the worse prognosis of dedifferentiated liposarcoma (DDLPS) compared to well-differentiated liposarcoma (WDLPS), it is imperative to understand how WDLPS tumors degenerate into DDLPS. Based on prior studies, we hypothesized that DDLPS progenitor cells can be found in patients with WDLPS. We performed 10x Genomics single-nuclear RNA sequencing on 15 samples from 11 patients with retroperitoneal liposarcoma, including 3 peritumoral fat samples, 4 WDLPS, 4 DDLPS, and 4 WDLPS with a DDLPS component. Sequencing was performed on a Singular G4. Data were integrated using scVI and analyzed using Scanpy. There were 74,511 nuclei passing quality control. Both DDLPS and WDLPS cells expressed high levels of MDM2 and CDK4, and inferred copy number variation (CNV) analysis was consistent with a chromosome 12q13-15 amplification. Major cell types were annotated using the expression of canonical markers: adipocytes: (ADIPOQ, LPL, negative for CDK4 and MDM2), adipocyte stromal progenitor (PI16, CD34, negative for CDK4 and MDM2), DDLPS cells (CDK4, MDM2), IGF1 PPARG progenitors (IGF1, PPARG), neuron-like progenitors (NLGN1, NKAIN3), WDLPS cells (ADIPOQ, LPL, positive for CDK4 and MDM2), and multiple immune and stromal cell types within the tumor microenvironment. Normal adipocyte stromal progenitor cells and normal adipocytes were present only in peritumoral samples. IGF1 PPARG progenitor cells and neuron-like progenitor cells, which expressed MDM2 and CDK4, were present in patients histologically diagnosed with DDLPS and WDLPS. Additionally, DDLPS cells were present in WDLPS patients. This suggests that precursor cells of DDLPS can be found in patients with no histological evidence of DDLPS. These cells may be involved in the dedifferentiation process. We are currently investigating these cells further with spatial transcriptomic profiling. Citation Format: James Paul. Agolia, Maria M. Korah, Angela D. Tabora, Amanda Goncalves, Chuner Guo, Rosyli F. Reveron-Thornton, Chia-Hsin Hsu, Biren Reddy, Wesley Bobst, Michael T. Longaker, Deshka S. Foster, Daniel Delitto. Single-nuclear RNA sequencing of retroperitoneal liposarcoma reveals progenitor cells of dedifferentiated liposarcoma in well-differentiated liposarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr A016.

Frank-ter Haar syndrome (FTHS) is an inherited disease associated with variants of the SH3PXD2B gene, encoding for the podosomal adaptor protein known as TKS4. FTHS is characterized by multiple skeletal abnormalities, developmental delay and severe craniofacial dysmorphology. This study provides an in-depth characterization of the calvarial phenotype of a mouse model of FTHS and investigates the potential underlying molecular and transcriptomic mechanisms. The Sh3Pxd2b(nee-/-)mouse presents with craniofacial malformations and disrupted suture patterning, as well as reduced osteoregeneration and decreased cell proliferation and migration observed both in vitro and in vivo, and impaired podosome formation. Transcriptomic analysis revealed downregulation of genes involved in ribosome biogenesis. Moreover, ribosomal RNA accumulates in cell protrusions of migrating cells. We established that the craniofacial phenotype of the Sh3Pxd2b(nee-/-) mouse is governed by impaired cell migration and proliferation due to dysfunctional podosome formation, particularly in neural crest-derived tissues. Transcriptomic and molecular data suggest altered ribosome-related processes, although further investigation is needed to clarify the underlying mechanisms.

Stratified epithelial differentiation involves transcriptional and proteomic remodeling. Here, multiomic profiling implicated ubiquitin and related posttranslational networks in differentiation dynamics. Systematic perturbation of ubiquitin-like machinery in primary human keratinocytes which uncovered opposite functions of neural-precursor-cell-expressed, developmentally down-regulated 8 (NEDD8) and small ubiquitin-related modifier 2 (SUMO2). Generation of conditional knockout mice established essential roles for NEDD8 in progenitor maintenance, skin regeneration, and inflammation, whereas SUMO2 was required for differentiation. Beyond ubiquitin-proteasome-concordant changes, NEDD8 directed proteomic regulation correlated with RNA abundance. Integration of immunoprecipitation- mass spectrometry with genome-wide suppressor screening revealed context-specific NEDDylation dependencies. Among effectors, heterogeneous nuclear ribonucleoprotein U (HNRNPU) emerged as a posttranscriptional regulator of epithelial cell state whose RNA binding repertoire was modulated by NEDDylation. Thus, NEDD8 and SUMO2 play opposite roles in epithelial homeostasis, regeneration, and inflammation, demonstrating multiple ways ubiquitin-like networks govern tissue homeostasis.

Abstract INTRODUCTION: Uterine leiomyosarcomas (ULMS) are rare, aggressive tumors with profound genomic heterogeneity, which has precluded the identification of effective targeted therapies. The overall purpose of this study was to investigate the transcriptomic and spatial landscape of ULMS to identify new therapeutic avenues. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on fresh ULMS tumors using the 10X Genomics platform and spatial transcriptomics on FFPE sections using the Singular G4X platform. Resulting cells were integrated with scVI or resolVI and annotated using canonical markers. Tumor signatures were correlated with patient outcomes using bulk RNA sequencing data and novel drugs predictions for each tumor cell subtype were computed using the scIDUC algorithm. RESULTS: ScRNA-seq was performed on 15 recurrent, metastatic ULMS tumors from 13 patients at the time of debulking surgery, which yielded 204,250 high quality cells. Spatial transcriptomics was performed on 29 sections from 10 patients, which yielded 2.3 million spatially resolved cells. Both assays revealed heterogenous tumor microenvironments comprised of several types of cells, including myeloid cells, lymphoid cells, endothelial cells, and tumor cells. Among the tumor cells, three prevalent subtypes emerged: 1) interferon-signaling cells that were distributed throughout sections, 2) mesenchyme-like cells arranged in nest-like configurations and around blood vessels, 3) ischemic cells with a high ribosomal signature organized around necrotic penumbras. Additionally, dedifferentiated stem-like cells with high expression of ESR1, PGR, and AR, along with Wnt signaling pathway markers, were scattered throughout tumor sections. These hormonal cells clustered into two subtypes on scRNA-seq: 1) those with high ESR1 and low AR/PGR and 2) those with low ESR1 and higher AR/PGR expression. These cells were the most sensitive to all interrogated drugs, including current first-line therapies gemcitabine, docetaxel, and doxorubicin. All other tumor subtypes were highly resistant to most drugs, though several alternative drug candidates uniquely targeting each tumor subtype were identified. Furthermore, by correlating with bulk RNA sequencing, each tumor subtype was shown to be associated with unique patient outcomes. AR and PGR hormone receptor-expressing cells correlated with improved patient survival, whereas ischemic cells correlated with the worst survival outcomes. CONCLUSIONS: We present a comprehensive atlas of ULMS, identifying several transcriptomic subtypes of tumor cells, including dedifferentiated stem-like hormonal cells that correlate with better drug sensitivity and improved patient outcomes. Findings from this study may further facilitate patient prognostication and guide targeted therapeutic management. Citation Format: Maria Moozhiyil Korah, James P. Agolia, Biren Reddy, Renceh A. Flojo, Amanda Gonçalves, Lilin Wang, Rosyli F. Reveron-Thornton, Chuner Guo, Beatrice Sun, Amanda R. Kirane, George Poultsides, Deshka Foster, R. Stephanie Huang, Gregory W. Charville, Michael T. Longaker, Daniel Delitto. Multidimensional transcriptomic alas of recurrent uterine leiomyosarcomas uncovers stem-like hormonal cells with high drug sensitivity and improved patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2201.

Calvarial sutures, the major growth centers for skull morphogenesis, are currently regarded as "niches" for calvarial stem cells. Our previous study has identified a skeletal stem/progenitor cell population resident within the suture mesenchyme. Moreover, we have shown that decrease and/or imbalance of their representation in the "niche" impact the fate of a non-fusing suture to fusing-suture and vice versa. Herein, taking advantage of an our established ex vivo calvarial suture explant model we investigated the impact triggered by FGF2, a pro-osteogenic and pro-angiogenic factor, on our skeletal stem/progenitor cell population resident in the suture mesenchyme. Multi-omics data integration combined with cell biology identifies dynamic changes in the representation of skeletal stem/progenitor cell population thus, unveiling within them functionally distinct populations with angiogenesis-competent properties. Findings altogether indicate that FGF2 stimuli may alter the suture "niche" homeostasis and that coordinate an osteogenesis-angiogenesis coupling within skeletal stem/progenitor cell sub-populations.

Abstract Skeletal stem cells (SSCs), originally identified in 2015, are increasingly understood to exhibit significant heterogeneity throughout the body. Cranial SSCs provide a unique model to investigate this diversity because cranial bones arise from both neural crest and mesoderm, unlike mesoderm-derived long bones. Here, we show that cranial SSCs possess anatomically defined transcriptomic and functional heterogeneity. Through comprehensive in vitro and in vivo functional assays combined with targeted gene expression analyses by qPCR, we demonstrate that cranial SSCs exhibit region-specific transcriptional signatures and lineage biases that influence their osteogenic and chondrogenic capacities. Temporal analysis further reveals that SSCs progressively outnumber progenitor cells with age, suggesting that the SSC-to-progenitor ratio may serve as an indicator of skeletal developmental and regenerative potential. Finally, we demonstrate that SSC heterogeneity critically influences bone regeneration in response to Bone Morphogenetic Protein-2 in vitro and in vivo, supporting the need for region-specific optimization of BMP-2-based regenerative therapies.

Progress toward anti-scarring therapies has been hampered by our limited understanding of fibroblast populations underlying fibrotic vs. regenerative healing. The site-dependent fibroblast heterogeneity acquired during development points to cell-intrinsic properties determining fibroblasts' scarring potential. Using a mouse wounding model, we observed that facial wounds heal with less scarring than scalp, ventral, and dorsal wounds. Single-cell RNA sequencing identified increased expression of Robo2 and downstream Eid1 in neural-crest-derived facial fibroblasts compared with fibroblasts from other sites. In fibroblast transplantation experiments, Robo2 and Eid1 promoted facial fibroblasts' reduced fibrotic potential. This is maintained by the inhibition of EP300 histone acetyltransferase, leading to a more transcriptionally silent chromatin landscape. Mimicking EID1's activity, small-molecule and transgenic EP300 repression in dorsal wounds promoted facial-like healing with reduced scarring. These data highlight the importance of ROBO2-EID1-EP300 signaling in facial wound healing and demonstrate our ability to modulate fibroblasts' embryologically determined fibrogenic potential to minimize scarring.

Translating scientific discoveries in tissue engineering and regenerative medicine (TE/RM) into clinically adopted therapies is hindered by fragmented development pipelines, regulatory and manufacturing challenges, and limited funding. Despite substantial investment by the U.S. National Institutes of Health (NIH), few NIH-funded TE/RM projects achieve commercialization or regulatory approval by the US Food and Drug Administration. The gap between academic innovation and clinical implementation is particularly evident in the dental, oral, and craniofacial (DOC) domain, where market and reimbursement constraints further restrict translation. To address these barriers, the National Institute of Dental and Craniofacial Research established the Dental, Oral and Craniofacial Tissue Regeneration Consortium (DOCTRC), comprising two nationwide Resource Centers tasked with guiding promising technologies from universities and small businesses through preclinical validation toward clinical adoption. This translational science case study outlines DOCTRC's translational model, highlighting lessons learned from five cohorts of interdisciplinary translational project teams, strategies for navigating manufacturing and regulatory pathways, and approaches for aligning academic innovation with clinical and market needs. The unique impact of the DOCTRC framework demonstrates how disciplined product development activities, non-dilutive funding mechanisms, and a comprehensive support ecosystem can accelerate technology translation, offering a scalable model for other biomedical fields.

Available mouse models for pancreatic ductal adenocarcinoma (PDAC) are limited by slow tumor development and failure to recapitulate key stromal and immune characteristics. Here, we present a protocol for generating a collagen hydrogel mouse model for orthotopic PDAC. We describe steps for embedding mouse pancreatic cancer cells in a dense collagen hydrogel and surgically implanting it into the mouse pancreas. Mouse PDAC tumors typically reach 1 cm in diameter by 10 days after implantation and show immune and stromal cell recruitment.For complete details on the use and execution of this protocol, please refer to Korah et al.1

Skeletal muscle injuries are common and some are able to regenerate due to satellite cells, the muscle stem cell population. However, in cases of severe muscle injury, complete tears, or muscle loss via trauma, muscles can undergo fibrosis and long-term compromise of their structure and function. The development of animal models has been key to understanding the pathways involved in muscle injury, fibrosis, and repair. In this review, we discuss the animal models currently used, with a focus on those most applicable to studying muscle fibrosis after traumatic injury. We summarize the approach, findings, and limitations of the most widely used models, including volumetric muscle loss, laceration, and myotoxin injection studies, and provide a brief description of ischemia/reperfusion, crush injury, freeze injury, and dystrophy models. We summarize the histological, cellular, molecular, and functional outcome measures commonly used in the field and outline areas for translation and future work. An expansion of current studies to specifically focus on muscle fibrosis will surely elucidate novel mechanisms for reducing debilitating fibrosis and promoting regeneration.

SIGNIFICANCE:Wound healing is an energetically demanding process that is easily disturbed by metabolic dysregulation. Metabolic dysregulation, induced by diabetes, obesity, insulin resistance, and various hormone imbalances, can disrupt each phase of wound repair, increasing the risk of post-operative complications, infection, wound dehiscence, and pathological scarring. We review the current evidence on the role of metabolic regulation in wound healing and highlight clinically relevant considerations for patient care. RECENT ADVANCES:Animal and human studies have advanced our understanding of how metabolic pathways influence inflammation, angiogenesis, fibroblast function, and extracellular matrix remodeling during wound healing. These insights have led to the development of novel therapies, including hormone-based topical agents and dressings that both sense and modulate metabolites during wound healing. CRITICAL ISSUES:Despite growing recognition of the role of metabolic syndromes and hormonal regulation in wound healing, these factors are insufficiently integrated into clinical wound management. Bridging this gap requires a clear understanding of how metabolic syndromes and hormonal derangements influence healing. FUTURE DIRECTIONS:The continued development of treatments that modulate metabolic and hormonal pathways may enhance wound healing while minimizing systemic risk. Clinicians should also integrate local metabolic optimization with medical and lifestyle management to create the optimal wound healing environment for patients.

Bulk RNA sequencing enables pan-cancer transcriptional analyses, but obscures cancer cell-specific programs due to admixture with nonmalignant cells, thereby limiting direct comparison between experimental models and primary tumors. Single-cell RNA sequencing (scRNA-seq) overcomes these limitations; however, the biological interpretability of public datasets is often compromised by variable data quality, inconsistent annotation, and atlas-scale aggregation strategies that prioritize data volume over biological coherence. We therefore developed a stringent integration framework that prioritizes representative malignant transcriptional states. Using Mahalanobis distance-based selection within batch-corrected latent space, we constructed a pan-cancer atlas comprising 135,424 high-quality malignant cells from 499 samples across 36 adult and pediatric cancers. Atlas-derived cancer signatures were used to determine tumor-cell line concordance and project ElasticNet models trained on DepMap CRISPR screens to infer cancer-specific gene dependencies. The scTumor Atlas establishes a scalable framework for tumor identity inference, cancer cell line benchmarking, and systematic identification of genetic vulnerabilities.

Abstract Introduction: Within the next five years, pancreatic ductal adenocarcinoma (PDAC) will become the second-highest cause of cancer death in the United States; even with surgical resection and chemotherapy, median overall survival remains less than three years. Spatial transcriptomic and proteomic analysis is one pathway toward therapeutic target discovery for PDAC. While previous spatial transcriptomic studies have uncovered remarkable intratumoral heterogeneity in primary and metastatic samples, most lack subcellular resolution and multiomic scale. Methods: Using the Singular G4X platform, we performed spatial multiomic analysis of 31 regions of interest in formalin-fixed, paraffin-embedded matched primary tumor and metastatic lymph nodes from eight patients. All patients had a pathological diagnosis of PDAC and received neoadjuvant chemotherapy at a single cancer center, and 7/8 patients showed pathological treatment effect with partial response to therapy. Data were analyzed in python. Results: After quality control, 2.4 million cells were integrated. Major cell types were manually annotated: acinar cells (CPB1+ GATM+), adipocytes (ADIPOQ+ PLIN1+), B cells (MS4A1+ HLA-DRA+), cancer-associated fibroblasts (COL1A1+ LUM+), plasma cells (JCHAIN+ IGHA1/IGHM+), macrophages (CD163+ CD68+), mast cells (KIT+), neuroendocrine cells (NRXN1+ NCAM1+), pericytes/endothelial cells (PECAM1+ RGS5+), smooth muscle cells (TAGLN+ MYH11+), and T cells (CD3D+ IL7R+). Tumor cells formed three distinct clusters: KRT19+ MUC1+ ductal cells, PIGR+ GATM+ ductal cells, and STAT1+ CD44+ cells (from one patient with sarcomatoid dedifferentiation). The predominant cell type in the tumor microenvironment, cancer-associated fibroblasts (CAFs) could be subclustered into inflammatory CAF (CXCL12-high IL6-high), mechanoresponsive CAF (PDGFRB-high ACTA2-high), and steady-state CAF phenotypes. Although we did not select regions of interest explicitly with tertiary lymphoid structures (TLSs) in mind, we found that 7/8 patients and 9/19 tumor sections contained putative TLSs, with 4 sections containing more than one TLS area. TLS morphology appeared similar to that of lymphoid aggregates in tumor-positive lymph nodes. A predominance of CAFs was also noted in the involved lymph nodes. B cells within TLSs stained positive for CD20 protein and expressed CXCR5 transcripts; they were surrounded by T cells that stained positive for CD3 and CD4/CD8 proteins. CXCR5 colocalized closely with its binding partner CXCL13, a known trigger of TLS formation. Conclusion: In a cohort of PDAC patients with lymph node metastasis, multiomic spatial analysis revealed TLSs in nearly all patients, suggestive of immune potential within the PDAC stroma. The CXCR5-CXCL13 axis should remain a target of active investigation in TLS formation. Citation Format: James P. Agolia, Chuner Guo, Rosyli F. Reveron-Thornton, Xiaomo Li, Maria Moozhiyil Korah, Angela Tabora, Byrne Lee, Amanda R. Kirane, George Poultsides, Brendan Visser, Gregory W. Charville, Michael T. Longaker, Deshka S. Foster, Daniel Delitto. Mapping lymphoid responses to tumor growth and lymph node metastasis: multiomic spatial analysis of pancreatic ductal adenocarcinoma reveals tertiary lymph node structures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2222.

Cancer-associated fibroblasts represent a functionally diverse and heterogeneous entity within the solid tumor microenvironment. Mitochondrial transfer from cancer cells to fibroblasts is now shown to act as a reprogramming stimulus, driving metabolic and functional differentiation of fibroblasts to support tumor growth.

Bronchopulmonary dysplasia is a common complication of preterm birth, driven in part by the inflammatory effects of supplemental oxygen on the immature lung. Although oxygen therapy is essential, it contributes to disrupted lung development but not all infants are equally susceptible. Using genetically diverse mouse models, we found that hyperoxia-sensitive mice exhibit a distinct innate immune response compared to resilient strains. Notably, the hyperoxia-sensitive C57BL/6J strain showed selective upregulation of TREM2 on lung macrophages and monocytes. Deletion of TREM2 in myeloid cells led to reduced inflammation, preserved alveolar structure and sustained cell proliferation in the developing lung following oxygen exposure. Mechanistically, TREM2 loss limited p53 activation, favoring cell-cycle arrest over apoptosis. These results identify TREM2 as a key driver of immune-mediated lung injury in neonatal hyperoxia and suggest it may be a promising therapeutic target for preventing or treating bronchopulmonary dysplasia in vulnerable preterm infants. Sajti and colleagues identify TREM2 as a critical factor in myeloid cells in response to hyperoxia-induced lung injury in neonates, finding that TREM2 deficiency protects mice from bronchopulmonary dysplasia.

Abdominal adhesions are a globally disruptive problem to patients and healthcare systems, with limited preventative strategies. Multiple discovery prophylactics have been evaluated previously for adhesions prevention with inadequate transfer to patient care. Clinical translation is fundamentally restricted by the ability of a discovery prophylactic to simultaneously navigate 3 key components of adhesions formation throughout the entire abdomen: the innate immune system, the coagulation system, and the local peritoneal cell populations. Furthermore, challenging handling characteristics and product restrictions have decreased the utilization of clinically available prophylactics by surgeons. The success of future adhesions prevention strategies must also be anchored in clinically valid animal modeling with attention towards future regulatory approval. The purpose of the present roadmap article is to provide a state-of-the-art review of adhesions pathophysiology, hydrogel development, animal modeling, and regulatory science, from which a framework for future developmental strategies may be outlined.