Dave, Maneesh; Dev, Atul; Somoza, Rodrigo A; Zhao, Nan; Viswanath, Satish; Mina, Pooja Rani; Chirra, Prathyush; Obmann, Verena Carola; Mahabeleshwar, Ganapati H; Menghini, Paola; Durbin-Johnson, Blythe; Nolta, Jan; Soto, Christopher; Osme, Abdullah; Khuat, Lam T; Murphy, William J; Caplan, Arnold I; Cominelli, Fabio (2024). MSCs mediate long-term efficacy in a Crohn's disease model by sustained anti-inflammatory macrophage programming via efferocytosis. npj Regenerative Medicine, 9(1), p. 6. Nature Publishing Group 10.1038/s41536-024-00347-1
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Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology |
UniBE Contributor: |
Obmann, Verena Carola |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2057-3995 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
22 Jan 2024 07:30 |
Last Modified: |
23 Jan 2024 16:22 |
Publisher DOI: |
10.1038/s41536-024-00347-1 |
PubMed ID: |
38245543 |
BORIS DOI: |
10.48350/191952 |
URI: |
https://boris.unibe.ch/id/eprint/191952 |
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