bims-migras 2026-02-01 papers

Issue of 2026–02–01
four papers selected by
Cliff Dominy

Cell Signal. 2026 Jan 23. pii: S0898-6568(26)00039-2. [Epub ahead of print]141 112389

Mechanisms and therapeutic potential of migrasomes in neurological disorders.

Simeng Zhang, Yanhua Yang, Tiancheng Zhang, Ye Pan, Qinggang Xu, Peng Lü.

Migrasomes, a recently identified class of organelles, form at the tips or intersections of retraction fibers during cell migration. These structures carry various bioactive cargoes, including proteins, mRNAs, and cytokines, and play significant roles in intercellular communication, immune regulation, and tissue homeostasis. As specialized membrane structures generated during cell migration, migrasomes are not only involved in physiological processes such as embryonic development and vascular homeostasis but are also critically implicated in the pathogenesis of neurological disorders. In this review, we outline the fundamental biological characteristics and functions of migrasomes, provide an in-depth analysis of their pathological mechanisms in neurological diseases, and evaluate their clinical potential as novel diagnostic biomarkers, drug delivery vehicles, and therapeutic targets. Overall, this review offers new perspectives for precision diagnostics and therapeutics of neurological diseases and lays a foundation for diagnosing and treating migrasome-related pathologies.

Keywords: Migrasomes; Neurological disorders; Pathological mechanisms; Therapeutic targets

DOI: https://doi.org/10.1016/j.cellsig.2026.112389

Front Cell Dev Biol. 2025 ;13 1666465

Dynamic crosstalk between Tspan4+ macrophage subsets and MSCs via migrasomes orchestrates fracture repair.

Siyu Zhang, Mengci Wang, Abudurexiti Kutibiding, Dandan Liu, Tuersunnayi Manafu, Wen Zhao, Yi Yang.

Background: The cell - cell communication between macrophages and mesenchymal stromal/stem cells (MSCs) holds pivotal importance in the fracture healing process. Considering the intricate nature of the in vivo bone regeneration microenvironment, elucidating the changes in different macrophage subsets within this microenvironment, as well as the cell - cell communication between these subsets and MSCs, is essential for the differentiation, recruitment, and regulation of MSCs. This study was designed to investigate the interactions between diverse macrophage subsets and MSCs during the fracture healing period.
Methods: Single - cell sequencing was utilized to analyze the expression of Tspan4+, Lyve1+, and Mpeg1+ in macrophages during fracture healing, along with the cell - interaction signals with MSCs. It was demonstrated that the cell - interaction signal transduction might be linked to migrasomes. Scratch assays and transwell assays were carried out to assess the migration capacity of MSCs affected by exosomes and migrasomes derived from Tspan4+Mpeg1+ macrophages. Micro-CT and immunofluorescence techniques were employed to observe the impacts of exosomes and migrasomes from 100 μg/mL Tspan4+Mpeg1+ macrophages on femoral fracture healing in mice.
Results: Through single - cell sequencing, it was ascertained that macrophages highly expressed Tspan4 during the fracture healing process and could be categorized into Tspan4+Lyve1+ macrophages and Tspan4+Mpeg1+ macrophages. By means of cell - communication analysis, Tspan4+Lyve1+ macrophages and Tspan4+Mpeg1+ macrophages were proposed to interact with MSCs via Gas6 - Axl and IL1b - IL1r1, respectively. Collectively, macrophage-derived migrasomes convey IL-1β to MSCs to activate AMPK, thereby enhancing BMSC migration and likely osteogenic priming during fracture repair. These findings identify migrasomes as a previously underappreciated conduit in macrophage-BMSC crosstalk and suggest a vesicle-based strategy to improve fracture healing.

Keywords: AMPK; IL1b; bone marrow mesenchymal stem cells; fracture healing; macrophages; migrasomes

DOI: https://doi.org/10.3389/fcell.2025.1666465

Acta Pharm Sin B. 2026 Jan;16(1): 1-12

Transmitophagy in the heart: An overview of molecular mechanisms and implications for pathophysiology.

Joshua Kramer, Eric Rohwer, Palaniappan Sethu, Min Xie, Timmy Lee, Victor Darley-Usmar, Jianhua Zhang.

Mitochondria are essential for meeting cardiac metabolic demands and their dysfunction is associated with heart failure and is a key mediator of cardiac ischemia-reperfusion injury. Cardiomyocytes engage integrated mechanisms to maintain mitochondrial function; however, chronic stress or disease can overwhelm this capacity. The removal of damaged mitochondria is mediated by a process known as mitophagy, which, together with mitochondrial biogenesis, plays a key role in maintaining mitochondrial quality control. Maintenance of mitochondrial quality control was initially thought to be autonomously regulated within each cellular population with little exchange between cells. However, recently the phenomenon of transmitophagy has been identified in which damaged mitochondria are transferred to neighboring cells for degradation. This review discusses the current understanding of transmitophagy in the context of heart injury, aging and disease, with particular emphasis on exophers, migrasomes, and tunneling nanotubes as pathways mediating cell-cell communication between cardiomyocytes, macrophages and fibroblasts. We further discuss the potential of targeting transmitophagy for cardioprotection and highlight key unanswered questions and challenges. Addressing these gaps may reveal novel strategies to preserve mitochondrial homeostasis and improve the outcomes of patients with cardiovascular disease.

Keywords: Cardiomyocytes; Exophers; Fibroblasts; Macrophages; Migrasomes; Mitophagy; TNTs; Transmitophagy

DOI: https://doi.org/10.1016/j.apsb.2025.11.030

J Nanobiotechnology. 2026 Jan 26.

Migrasomes constrained by a homologous-targeting photodynamic nanoplatform: enhancing intratumoral CD8+ T-cell-associated antitumor immunity in oral squamous cell carcinoma.

Lejia Zhang, Hui Gao, Wanting Jia, Fangyang Shi, Xun Chen, Kuangwu Pan, Runze Li, Jie Wu, Kuntao Li, Wei Zhao, Yi He, Dongsheng Yu.

Photodynamic therapy (PDT) is an effective adjunct treatment for oral squamous cell carcinoma (OSCC). Enhancing photosensitizer targeting and inducing effective cytotoxic T-cell responses through photoimmunotherapy have become key strategies to improve PDT efficacy. Migrasomes, as vesicular structures assembled by TSPAN4 and cholesterol microdomains, are implicated in immune escape and are emerging as sensitization targets for PDT. Here, we report a biomimetic nanoplatform, MOF-919@CCM, that combines enhanced tumor-cell membrane adhesion with light-controlled cholesterol degradation. Cloaking with a homologous cancer-cell membrane (CCM) imparts specific adhesion to tumor cells and improves targeted delivery of the photosensitizer. Moreover, the transition-metal nodes of MOF-919 exhibit peroxidase- and catalase-like activities that alleviate tumor hypoxia and, under laser irradiation, effectively reduce cellular cholesterol levels. Experiments further revealed that PDT based on MOF-919@CCM markedly suppresses migrasome formation via effective degradation of cholesterol and promotes CD8⁺ T-cell infiltration and cytotoxic activity against tumor cells. This work develops a targeted PDT approach using MOF-919@CCM and provides a new strategy for the immunotherapy of OSCC.

Keywords: CD8; Homologous targeting; Immune checkpoint; Migrasome; Oral squamous cell carcinoma; Photodynamic therapy

DOI: https://doi.org/10.1186/s12951-026-04037-6