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| Status |
Public on Nov 12, 2025 |
| Title |
Bioengineered Extracellular Vesicles Co-delivering PD-L1 and miR-27a-3p Synergistically Reprogram T cells To Treat Inflammatory Bowel Disease [scRNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Current treatments for inflammatory bowel disease (IBD) primarily rely on systemic immunosuppression, which often exhibits limited efficacy and off-target toxicity. Here we present a bioengineered extracellular vesicle (EV) platform designed for inflammatory bowel-targeted delivery of dual-action therapeutics, enabling precise modulation of T cell responses to enhance IBD treatment efficacy. EVs derived from Wharton’s jelly mesenchymal stem cells ( WJ-MSCs) were engineered to display membrane-bound PD-L1 and encapsulate miRNA 27a-3p (miR-27a-3p). The platform leverages WJ-MSCs’ intrinsic immunomodulatory properties and CXCR4-mediated recruitment to inflamed tissues. PD-L1 not only promotes immunosuppression of effector T cells, but also may enhance EV retention within inflamed sites. Meanwhile, miR-27a-3p shifts the Th17/Treg balance from a pro-inflammatory Th17 phenotype toward an anti-inflammatory Treg phenotype by targeting prohibitin 1. Bulk RNA sequencing of human CD4⁺ T cells treated with the EVs revealed downregulated of Th1/Th17-associated transcripts. In a humanized mouse model of colitis, EV treatment significantly reduced disease severity, diminished intestinal T cell infiltration, and restored mucosal integrity. Single-cell RNA sequencing demonstrated expansion of Treg cells and contraction of effector memory subsets, indicating durable immune modulation. This engineered EV platform represents a novel therapeutic paradigm that combines inflamed tissue targeting and dual immunomodulatory mechanisms to restore immune tolerance in IBD, addressing key limitations of conventional immunosuppressive approaches.
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| Overall design |
RNA sequencing was performed on CD4⁺ T cells from spleens of IBD humanized mouse models (human graft), CD4⁺ T cells from human PBMCs, WJ-MSCs, and WJ-MSC–derived exosomes. The study includes single-cell RNA-seq, bulk mRNA-seq, and small RNA-seq to assess transcriptomic and miRNA profiles in the context of IBD and engineered exosome therapy.
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| Contributor(s) |
Oh M, Park H, Yu K |
| Citation missing |
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| Submission date |
Jul 15, 2025 |
| Last update date |
Nov 13, 2025 |
| Contact name |
Mi-Kyung Oh |
| E-mail(s) |
ipomk@snu.ac.kr
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| Organization name |
Seoul National University
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| Department |
Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences
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| Street address |
1 Gwanak-ro, Gwanak-gu
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| City |
Seoul |
| ZIP/Postal code |
08826 |
| Country |
South Korea |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1291753 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE302696_RAW.tar |
482.4 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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