bims-migras 2025-11-23 papers

Issue of 2025–11–23
five papers selected by
Cliff Dominy

J Neuroinflammation. 2025 Nov 15. 22(1): 271

BM-MSC-derived migrasomes reverse stroke-induced thymic atrophy and immunosuppression via Pin1 delivery to thymic epithelial cells.

Haotong Yi, Mengyan Hu, Liling Yuan, Xiaotao Su, Shilin Wu, Tiemei Li, Shisi Wang, Xinmei Kang, Yuxin Liu, Zhiruo Liu, Qin Qin, Weihua Yu, Yifan Li, Wei Qiu, Wei Cai, Zhengqi Lu.

Acute ischemic stroke triggers immunosuppression, yet existing therapies struggle to balance neuroprotection with poststroke immunosuppression. We demonstrated that bone marrow mesenchymal stem cells (BM-MSC) reverse stroke-induced thymic atrophy by promoting T-cell differentiation and restoring peripheral T-cell populations. Bulk RNA sequencing of BM-MSC-treated thymuses revealed enhanced proliferative signatures. Mechanistically, BM-MSC secrete migrasomes (organelles derived from migrating cells) that traverse the blood‒thymus barrier. Single-cell RNA sequencing analysis demonstrated that migrasome-mediated proliferation occurred specifically in medullary thymic epithelial cell I (mTECI) subpopulations. Proteomic profiling via liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) identified Pin1-a cell cycle regulator-as the predominant cargo in BM-MSC-derived migrasomes. In vivo and in vitro studies confirmed migrasome-mediated thymic epithelial proliferation, T-cell niche reconstruction, and immune homeostasis restoration. Migrasome monotherapy improved neurological deficits and survival rates in stroke model mice, demonstrating dual neuroprotective-immunomodulatory efficacy. This work addresses the clinical dilemma between neuroprotection and immunosuppression alleviation, establishing migrasomes as a cell-free therapeutic strategy for poststroke immunotherapy.

Keywords: BM-MSC; Immunosuppression; Migrasomes; Stroke; Thymic epithelial cells; Thymus

DOI: https://doi.org/10.1186/s12974-025-03604-2

Biomaterials. 2025 Nov 11. pii: S0142-9612(25)00772-0. [Epub ahead of print]328 123853

A mechanosensitive fluorescent probe for visualizing migrasome mechano-spatiotemporal dynamics.

Kongqi Chen, Qiong Liu, Mengjie Wang, Chuen Kam, Mingmin Zhang, Zhiming Wang, Sijie Chen.

Migrasomes, recently identified as extracellular vesicles formed along the retraction fibers (RFs) in migrating cells, are evident in damaged mitochondria clearance, intercellular signaling, embryonic development, and pathological progression of diseases. During migrasome biogenesis, signaling cues and membrane dynamics interplay with each other in the maturation, expansion, and detachment of migrasomes from RFs. Membrane tension plays a crucial role in migrasome dynamics, and tools for monitoring the dynamic mechanical properties of migrasomes are highly desired. In this study, we developed and characterized a novel mechanosensitive but viscosity-insensitive fluorescent probe, named OT2SQ, for real-time investigation of migrasome dynamics in living cells. OT2SQ is a twisted small molecule with multiple rotatable units, exhibiting longer fluorescence lifetimes in response to increased membrane tension but showing no response to altered viscosity. Using time-lapse fluorescence lifetime imaging, we identified distinct modes of migrasome biogenesis and detachment from retraction fibers, each associated with unique membrane tension dynamics. Furthermore, phasor-FLIM analysis revealed alterations in migrasome membrane tension during content release and internalization processes. This study introduces a versatile fluorescent tool for real-time monitoring of migrasome morphology, spatiotemporal distribution, and membrane tension dynamics.

Keywords: Aggregation-induced emission; Fluorescence lifetime imaging; Membrane tension; Migrasome dynamics; Migrasome imaging

DOI: https://doi.org/10.1016/j.biomaterials.2025.123853

Neurosci Bull. 2025 Nov 18.

Agomelatine Targets Aquaporin-4 Polarization to Rescue Glymphatic Dysfunction in Parkinson's Disease.

Shisi Wang, Dan Wu, Guoming Chen, Jun Yuan, Lu Zheng, Xuehong Huang, Xu Liu, Zhuang Kang, Yiwei Feng, Jialu Zhang, Wei Cai, Zhengqi Lu, Lei Wei.

Melatonin deficiency in Parkinson's disease (PD) patients correlates with impaired glymphatic function as measured by diffusion tensor imaging along the perivascular space (DTI-ALPS) index, suggesting circadian-regulated waste clearance as a therapeutic target. Unlike previous studies focusing on agomelatine's (AGM) antidepressant and sleep-regulating properties, we demonstrate its novel mechanism in PD treatment through glymphatic enhancement. Retrospective clinical analysis of PD patients revealed that AGM administration restored glymphatic function and improved motor performance. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced (MPTP) PD models, AGM alleviated glymphatic dysfunction and anxiety-like behaviors while reducing PD pathology. Crucially, AGM promoted aquaporin-4 (AQP4) polarization at astrocytic endfeet, as evidenced by RNA sequencing showing enhanced gap junction-related gene expression. The brain and muscle ARNT-like 1 (BMAL1)-mediated transcriptional regulation emerged as the key pathway underlying these effects. Our findings establish AGM as the first melatoninergic agent targeting the glymphatic-AQP4 axis in PD, shifting therapeutic strategies from symptomatic relief to disease modification. This provides clinical rationale for repurposing circadian regulators to decelerate PD progression through enhanced protein clearance.

Keywords: Agomelatine; Aquaporin-4; Glymphatic system; Parkinson’s disease

DOI: https://doi.org/10.1007/s12264-025-01543-9

Adv Sci (Weinh). 2025 Nov 21. e04871

Bisphenol B Exposure Induces Miscarriage by Suppressing Migration/Invasion and Migrasome Formation.

Wenxin Huang, Manli Wang, Yi Sun, Xiaoping Yue, Xun Li, Yanbing Lin, Geng Guo, Depeng Zhao, Qigang Fan, Xiaoling Ma, Zhihong Zhang, Shuaishuai Xing, Xiaoting Shen, Huidong Zhang.

Unexplained miscarriage (UM) remains challenge due to unclear pathogenesis and biological mechanisms. BPB (Bisphenol B), an extensively used endocrine disrupting chemical, has been widely detected out in human. Migrasomes are newly identified cellular organelles with a large number of unknown functions. However, whether and how BPB exposure may suppress migrasome formation (MF) to induce miscarriage are completely unknown. In this study, it is found that higher urinary BPB levels are associated with the suppressed MF in villous tissues and unexplained miscarriage. It is further confirmed that BPB exposure suppresses MF in the mouse placenta and thus induces miscarriage. Supplement with Pkca or Tspan4, two essential proteins for migration/invasion (MI) and MF, can efficiently treat against BPB-induced miscarriage. In biological mechanisms, BPB up-regulates ER levels, enhances its interactions with the lnc-HZ04 promoter region, and thus promotes ER-mediated lnc-HZ04 transcription. Subsequently, lnc-HZ04 suppresses TCF4-mediated PKCA transcription and subsequently suppresses MI and MF. Collectively, this study not only identifies BPB as a novel risk factor for unexplained miscarriage, discovers novel pathogenesis and biological mechanisms in BPB-induced miscarriage, but also provides potential targets for treatment against unexplained miscarriage.

Keywords: PKCA/RAC1/CXCL12; environmental BPB (bisphenol B); female trophoblast cell migration/invasion; migrasome formation; non‐coding RNA lnc‐HZ04; unexplained miscarriage

DOI: https://doi.org/10.1002/advs.202504871

Sci Rep. 2025 Nov 18. 15(1): 40532

Weihang Li, Yanrong Cao, Xin Sun, Ting Wang, Panling Xu, Ping Li.

The onset of pancreatic cancer is insidious, and the early symptoms are similar to those of common gastrointestinal diseases, which leads to easy neglect and misdiagnosis, which greatly affects the accuracy of survival prediction. Cell migration is the hallmark of malignant tumor and the key step of metastasis. Migrasome are involved in embryonic development, immune response, angiogenesis, inflammatory response, wound healing, and cancer metastasis in vivo. Considering the unknown association between migrasome and lncRNAs in pancreatic cancer, the purpose of this study was to identify migrasome-related lncRNAs (MRLs) and explore their prognostic value. In this study, we first analyzed the Pancreatic adenocarcinoma (PAAD) data in The Cancer Genome Atlas(TCGA) database and identified the correlation between MRLs and pancreatic cancer prognosis and immune infiltrating landscape. Secondly, four MRLs (MED14OS, AC141930.2, Z97832.2, LINC01091) were selected to construct a risk model as a prognostic feature. Kaplan-Meier survival analysis, Cox regression analysis, Nomogram and Time - dependent Receiver Operating Characteristic (ROC) Curve were then used to verify the accuracy of the model. And then, the Prognostic Risk Model were used in clinical to validate the accuracy. Finally, the correlation of immune score, tumor immune cell infiltration, tumor mutation load, tumor immune escape, and drug sensitivity of the risk model was systematically analyzed. The risk-prognosis model of MRLs was constructed. Survival analysis showed that the survival rate of high-risk subtypes was lower than that of low-risk subtypes. MRL features were an independent prognostic predictor, and the area under the subject working curve (AUC) for 1-year, 3-year, and 5-year were 0.667, 0.780, and 0.865, respectively. Prognosis MRLs is related to immune infiltrating landscape and can reflect the immune status, immune response, tumor mutation burden and drug sensitivity of pancreatic cancer patients. At the same time, this model can distinguish clinical patients well. The results of this study construct a predictive model of pancreatic cancer associated with migrasome, and clarify the relevance of this model to immunotherapy and so on. It provides a new idea for improving immunotherapy and drug therapy.

Keywords: Immune microenvironment; Migrasome-related LncRNA; PAAD; Prognosis; Risk model

DOI: https://doi.org/10.1038/s41598-025-24226-x