ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Apoptosis in mesenchymal stromal cells activates an immunosuppressive secretome predicting clinical response in Crohn's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Randomized phase 2b dose-escalation trial of stem cell therapy with laromestrocel for aging frailty.Cell stem cell · 2026Trial
- Adipose tissue-derived mesenchymal stem cells combined with prednisone synergistically ameliorate autoimmune hepatitis in mice.Stem cell research & therapy · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Hypoxia-induced metabolic and apoptotic reprogramming enhances immunomodulation in Wharton's jelly mesenchymal stem cells.iScience · 2026Article
- Mesenchymal Stem Cells Derived Extracellular Vesicles in Inflammatory Bowel Disease: Therapeutic Efficacy and Bioengineering Applications.International journal of nanomedicine · 2026Review
- Limitations in the clinical translation of mesenchymal stromal cells: standardisation, heterogeneity and the recipient.Frontiers in cell and developmental biology · 2026Review
- Assessment of Vedolizumab and UC-MSC interaction and therapeutic potential in acute graft-versus-host-disease.Frontiers in cell and developmental biology · 2026Article
- Mesenchymal stromal cells induce neutrophil aggregation and extracellular vesicle storms for systemic lupus erythematosus.Signal transduction and targeted therapy · 2025Article
- Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies.Signal transduction and targeted therapy · 2025Review
- Palmitate enhances MSC immunomodulation of human macrophages via the ceramide/CCL2 axis in vitro.Stem cell research & therapy · 2025Article
- Uncovering the bequeathing potential of apoptotic mesenchymal stem cells via small extracellular vesicles for its enhanced immunomodulatory and regenerative ability.Stem cell research & therapy · 2025Article
- Proinflammatory cytokines sensitise mesenchymal stromal cells to apoptosis.Cell death discovery · 2025Article
- Apoptotic mesenchymal stem cells and their secreted apoptotic extracellular vesicles: therapeutic applications and mechanisms.Stem cell research & therapy · 2025Review
- Fate and long-lasting therapeutic effects of mesenchymal stromal/stem-like cells: mechanistic insights.Stem cell research & therapy · 2025Review
- Mesenchymal stromal cells as rescue therapy in biologic-refractory psoriasis: insights from a case series.Frontiers in immunology · 2025Article
- MSC Manufacture.Advances in experimental medicine and biology · 2025Review
- Mesenchymal stromal cells reduce inflammation and improve lung function in a mouse model of cystic fibrosis lung disease.Scientific reports · 2024Article
- Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue.International journal of molecular sciences · 2024Article
- New functions of oxylipins released by pyroptotic cells.Acta pharmaceutica Sinica. B · 2024Article
- Concurrent hypoxia and apoptosis imparts immune programming potential in mesenchymal stem cells: Lesson from acute graft-versus-host-disease model.Stem cell research & therapy · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
In vivo apoptosis of human mesenchymal stromal cells (MSCs) plays a critical role in delivering immunomodulation. Yet, caspase activity not only mediates the dying process but also death-independent functions that may shape the immunogenicity of apoptotic cells. Therefore, a better characterization of the immunological profile of apoptotic MSCs (ApoMSCs) could shed light on their mechanistic action and therapeutic applications. We analyzed the transcriptomes of MSCs undergoing apoptosis and identified several immunomodulatory factors and chemokines dependent on caspase activation following Fas stimulation. The ApoMSC secretome inhibited human T cell proliferation and activation, and chemoattracted monocytes in vitro. Both immunomodulatory activities were dependent on the cyclooxygenase2 (COX2)/prostaglandin E2 (PGE2) axis. To assess the clinical relevance of ApoMSC signature, we used the peripheral blood mononuclear cells (PBMCs) from a cohort of fistulizing Crohn's disease (CD) patients who had undergone MSC treatment (ADMIRE-CD). Compared with healthy donors, MSCs exposed to patients' PBMCs underwent apoptosis and released PGE2 in a caspase-dependent manner. Both PGE2 and apoptosis were significantly associated with clinical responses to MSCs. Our findings identify a new mechanism whereby caspase activation delivers ApoMSC immunosuppression. Remarkably, such molecular signatures could implicate translational tools for predicting patients' clinical responses to MSC therapy in CD.
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