bims-migras 2026-09-13 papers

Issue of 2026–09–13
three papers selected by
Cliff Dominy

Mater Today Bio. 2026 Oct;40 103607

Engineering migrasome-inspired extracellular vesicles through temperature stimuli on thermoresponsive substrate for retraction fiber formation and hypoosmotic vesiculation.

Koki Yoshikawa, Shogo Saito, Mina Okochi.

Migrasomes, recently identified extracellular vesicles, play critical roles in physiological processes such as tissue remodeling and intercellular communication. However, their generally low and cell-type-dependent biogenesis limits their broader applications. Here, a simple and scalable method for producing migrasome-inspired vesicles, termed osmotically-induced migrasome-like vesicles (OsMigs), through temperature stimuli-induced retraction fiber on thermoresponsive polymer-modified substrates and hypoosmotic vesiculation was developed. A two-step cooling treatment of 4 °C and 20 °C on the poly (N-isopropylacrylamide)-modified substrate coincidently led to the appearance of retraction fibers. This approach reproducibly achieved more than an order-of-magnitude increase in vesicle yield compared to migrasome biogenesis in normal human dermal fibroblasts, and is broadly applicable to multiple adherent cell types, including even those that do not naturally form migrasomes. OsMigs are enriched in migrasome-associated markers, including tetraspanin-4, integrin α5, and cholesterol, and encapsulate bioactive cytokines. Functionally, OsMigs significantly promote fibroblast migration and angiogenesis in vitro. Importantly, this entirely physical, enzyme- and chemical-treatment-free approach provides a scalable and reproducible platform for engineering migrasome-inspired EVs, opening new avenues for studying extracellular vesicle-mediated signaling and laying the foundation for future EV-based therapeutic applications.

Keywords: Extracellular vesicles; Migrasome; Poly-N-isopropylacrylamide; Wound healing

DOI: https://doi.org/10.1016/j.mtbio.2026.103607

Cancer Biol Med. 2026 Sep 08. pii: j.issn.2095-3941.2025.0803. [Epub ahead of print]

Migrasome-propagated ITGβ3-TGFβ1 circuit orchestrates breast cancer brain metastasis by reprogramming the microglial niche.

Song Wang, Xinmiao Xian, Guohao Gu, Jianran Guo, Meng An, Dongbao Li, Qian Wang, Xuefang Huang, Shen Chen, Wei Zhang, Bo Fu.

OBJECTIVE: The dismal prognosis of breast cancer brain metastasis (BCBM) is attributed to a maladapted tumor microenvironment. This study was aimed at deciphering the role of novel intercellular communicators, tumor-derived migrasomes, in driving BCBM progression, with a focus on their ability to co-opt brain-resident microglia.
METHODS: Migrasomes were isolated and characterized from brain-tropic (231-BR; Mig-BCBM) and parental breast cancer cells, patient-derived metastatic breast cancer tissues, and mice BCBM tissues. The functional axis was delineated through an integrative approach encompassing proteomics, in vitro co-culture systems, in vivo brain colonization assays, genetic perturbations, and a pharmacological intervention with the clinical-stage TGFβR1 inhibitor galunisertib.
RESULTS: Mig-BCBM were internalized by microglia, thus triggering their repolarization to a pro-tumorigenic, M2-like state, both in vitro and in vivo. Proteomic profiling identified integrin β3 (ITGβ3) as a key regulator selectively packaged into Mig-BCBM. Mechanistically, migrasomal ITGβ3 activated the PI3K/AKT pathway in microglia, thus driving M2 polarization. These reprogrammed microglia secreted high levels of TGFβ1, which in turn fostered a metastatic niche by inducing Smad2/3-dependent epithelial-mesenchymal transition (EMT) in tumor cells. Crucially, we uncovered a self-amplifying feedforward loop in which microglial-derived TGFβ1 transcriptionally upregulates TSPAN4 via EGR1 in cancer cells, thus enhancing migrasome biogenesis and subsequent ITGβ3 loading. Disrupting this loop with galunisertib potently inhibited BCBM outgrowth and colonization in vivo, without systemic toxicity.
CONCLUSIONS: This study identified a targetable circuit in BCBM wherein tumor-derived migrasomes, via ITGβ3, engage microglia in a TGFβ1-centered crosstalk. Because this self-reinforcing ITGβ3-TGFβ1 axis sustains the pro-metastatic niche, its disruption might provide a rational therapeutic strategy.

Keywords: Breast cancer brain metastasis; ITGβ3; TGFβ1; TSPAN4; microglia; migrasome

DOI: https://doi.org/10.20892/j.issn.2095-3941.2025.0803

Bioact Mater. 2027 Feb;68 1-26

Quercetin-derived carbon dots-modified ZIF-8 and M2 macrophage-derived migrasomes-functionalized microenvironment-responsive nanocomposite hydrogel for osteoporotic bone defects regeneration.

Han Yin, Yuguo Li, Yanbin Zhu, Zineng Yan, Yuanyuan Han, Fangyan Cheng, Jinglue Hu, Jiangtao Ma, Xin Xing, Cao Yang, Hongtao Tian, Wei Chen, Yingze Zhang.

The impaired regenerative capacity of osteoporotic individuals poses a significant challenge to the repair of bone defects. In the osteoporotic microenvironment, low pH, excessive reactive oxygen species (ROS), and chronic inflammation create a self-perpetuating vicious cycle that impedes healing. However, conventional therapies fail to sustainably improve the damaged microenvironment. Here, a pH/ROS dual responsive nanocomposite hydrogel (Z-QCDs@M2-Migs@OHA-PP) was developed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), quercetin-derived carbon dots (QCDs) loaded ZIF-8 (Z-QCDs) and M2 macrophage-derived migrasomes (M2-Migs), which possesses intrinsic antioxidant and osteogenic differentiation-promoting capabilities. Due to the presence of dynamic. Schiff base bonds and boronate bonds, the hydrogel exhibited injectability and pH/ROS dual responsiveness. OHA-PP releases Z-QCDs and M2-Migs on demand in response to changes in pH and ROS levels. Z-QCDs exhibit strong antioxidant and nanozyme activity, capable of scavenging ROS, suppressing inflammatory responses, and promoting M2 macrophage polarization. Furthermore, the introduction of M2-Migs as an osteogenic activator further enhances the capacity for osteogenic differentiation. Transcriptomic and Western blot analyses revealed that the hydrogel promotes osteogenic differentiation by activating the PI3K-AKT signaling pathway. In a mouse osteoporotic bone defect model, the nanocomposite hydrogel effectively inhibited ferroptosis, modulated inflammation, and promoted new bone formation. Therefore, this hydrogel system, which combines therapeutic rationale with microenvironmental regulation, offers a promising strategy for the regeneration of osteoporotic bone defects.

Keywords: Dual responsive hydrogel; M2 macrophage-derived migrasomes; Osteoporotic bone defect; Quercetin-derived carbon dots; ZIF-8

DOI: https://doi.org/10.1016/j.bioactmat.2026.07.029