Effect of Crohn's disease mesenteric mesenchymal stem cells and their extracellular vesicles on T‐cell immunosuppressive capacity
Bibliographic record
Abstract
Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal intestinal tract and has characteristic hypertrophic adipose changes observed in the mesentery. To better understand the role of the mesentery in the pathophysiology of Crohn's disease (CD), we evaluated the immunomodulatory potential of mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) derived from Crohn's patients. MSCs and EVs were isolated from the mesentery and subcutaneous tissues of CD patients and healthy individuals subcutaneous tissues, and were analysed for differentiation, cytokine expression, self-renewal and proliferation. The varying capacity of these tissue-derived MSCs and EVs to attenuate T-cell activation was measured in in vitro and an in vivo murine model. RNA sequencing of inflamed Crohn's disease mesentery tissue revealed an enrichment of T-cell activation compared to non-inflamed subcutaneous tissue. MSCs and MSC-derived EVs isolated from Crohn's mesentery lose their ability to attenuate DSS-induced colitis compared to subcutaneous tissue-derived cell or EV therapy. We found that treatment with subcutaneous isolated MSCs and their EV product compared to Crohn's mesentery MSCs or EVs, the inhibition of T-cell proliferation and IFN-γ, IL-17a production increased, suggesting a non-inflamed microenvironment allows for T-cell inhibition by MSCs/EVs. Our results demonstrate that Crohn's patient-derived diseased mesentery tissue MSCs lose their immunosuppressive capacity in the treatment of colitis by distinct regulation of pathogenic T-cell responses and/or T-cell infiltration into the colon.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".