Angiogenesis最新文献

Microvascular network formation is governed by a variety of factors, with interstitial flow (IF) playing a pivotal role. However, the impact of multidirectional IF (MDIF) on microvascular network development remains insufficiently explored. In this study, we developed a platform consisting of a Square chip capable of generating MDIF and a deep learning-based Vasculature-on-a-Chip Analysis Tool (VoCAT) for high-efficient analysis of vascular morphology on the chip. Using this platform, we demonstrated that microvascular networks formed on the Square chip exhibited intricate structural features with enhanced functionality. We also demonstrated its utility in modeling a tumor microenvironment with complex microvascular networks and observed enhanced tumor cell migration. This study provides the first evidence that MDIF promotes microvascular network formation, offering new perspectives for advanced in vitro vascular and disease research.

Diabetic retinopathy (DR) is characterized by chronic retinal inflammation and vascular remodeling that can threaten vision. Most current treatments are administered intravitreally and target vascular endothelial growth factor A (VEGF) but are often ineffective. Nevertheless, few alternative treatments, and no oral DR therapies, exist. Although IL-1β, TNFα, and IL-8 are upregulated along with VEGF within eyes with DR, they are not therapeutically targeted. IL-8 levels correlate with DR progression and resistance to anti-VEGF therapy, suggesting VEGF-independent contributions of IL-8-receptor signaling to DR. IL-1β and TNFα, in turn, enhance expression of pro-angiogenic CXCR2 ligands (e.g. IL-8, CXCL1) in human Müller cells (hMC). Despite investigation of CXCR2 roles in several angiogenic and fibrotic diseases, CXCR2 inhibitors have not been explored in DR models. In this study, we show protein upregulation of IL-8 and CXCL1, but no detectable VEGF in conditioned media (CM) from IL-1β and TNFα-stimulated hMC. Stimulation of human retinal microvascular endothelial cells (hRMEC) with this human Müller cell-conditioned media (hMC-CM), as well as directly with IL-8, upregulated hRMEC proliferation and migration. CXCR2 inhibition reduced pro-angiogenic hRMEC responses to hMC-CM and IL-8. Likewise, in vivo, in the oxygen-induced retinopathy (OIR) model, either genetic (Cxcr2^-/-) or pharmacologic (SB225002) CXCR2 inhibition reduced pre-retinal neovascularization without altering avascularity or VEGF expression. These findings suggest that: (a) Müller cells may link inflammatory and angiogenic responses in the retina, (b) CXCR2 activation may contribute to DR, and (c) CXCR2 inhibitors may be repurposed to reduce pre-retinal neovascularization, a key feature of proliferative DR.

This letter aims to provide a forward-looking analysis of the recent preclinical study by Ou et al. (Angiogenesis, 2025) on the efficacy of the multi-kinase inhibitor KC1036 in Ewing sarcoma (ES).We conducted a critical appraisal of the reported data, focusing on the dual anti-angiogenic and direct anti-tumor mechanisms of KC1036. The analysis is contextualized within the current understanding of ES pathogenesis and treatment resistance.The original study compellingly demonstrates that KC1036, by concurrently inhibiting VEGFR and FGFR signaling, effectively suppresses ES growth. While these findings are promising, they raise pivotal questions for future investigation. Key considerations include the precise mechanistic interplay between KC1036 and the EWSR1-FLI1 oncogenic driver, the potential evolution of resistance despite multi-targeted inhibition, and the critical assessment of the agent’s therapeutic index.KC1036 represents a rational and potent therapeutic candidate for ES. The primary challenges ahead lie in delineating its molecular mechanisms of action beyond angiogenesis, prospectively defining resistance pathways to guide combination therapies, and rigorously evaluating its safety profile to ensure successful clinical translation. This letter outlines these priorities to stimulate further research.

The renal vasculature consists of highly specialized blood vessels with distinct physiological functions. Defining their transcriptional signatures and tracing their developmental ontogeny has thus far been challenging due to a lack of regionally specific endothelial biomarkers. Here, we performed single nuclear RNA sequencing (snucRNA-Seq) to interrogate the transcriptional heterogeneity of embryonic renal endothelial cells (ECs). We identified ten endothelial subtypes, and validated regionally restricted expression of novel marker genes of glomeruli, arteries, vasa recta, and immature capillary subtypes using multiplex RNAscope. We also define previously uncharacterized and heterogeneous molecular signatures of the immature renal vasculature, including putative endothelial progenitors. We interrogate biological characteristics of immature EC types using a variety of in vivo tools. Lineage tracing of Esm1-expressing cells reveals the previously unrecognized multi-origin and multi-clonal endothelial tip cell contribution to the glomerular vasculature. Together, this study provides a validated, tool-focused developmental atlas of the murine renal vasculature and elucidates novel cellular mechanisms of nephron vascularization.

The recent study by Santos-De-La-Mata et al. (Angiogenesis 28(4): 482025, 2025) provides critical evidence that adipose-derived stem cells (ASCs) from patients with chronic spinal cord injury (SCI) and pressure injuries (PIs) exhibit significantly impaired vasculogenic potential.1 Their comparative analysis revealed deficits in key pro-angiogenic functions, including reduced proliferation, migration, tube formation, and secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in SCI/PI-derived ASCs compared to healthy controls. These in vitro findings were corroborated by a diminished capacity to support neovascularization in an in vivo Matrigel plug assay. This cellular dysfunction underscores a fundamental mechanism contributing to refractory wound healing in this patient population and critically challenges the efficacy of autologous ASC-based therapies. This analysis discusses these findings in the context of chronic inflammatory microenvironments and epigenetic regulation,2,3 and explores potential strategies to overcome this impairment, including allogeneic cell sources4,5 and pre-conditioning techniques to rejuvenate patient-derived cells.6 The work of Santos-De-La-Mata et al. establishes a vital foundation for developing more effective, personalized regenerative medicine approaches for complex chronic wounds.