التفاصيل البيبلوغرافية
| العنوان: |
MSCs mediate long-term efficacy in a Crohn’s disease model by sustained anti-inflammatory macrophage programming via efferocytosis |
| المؤلفون: |
Maneesh Dave, Atul Dev, Rodrigo A. Somoza, Nan Zhao, Satish Viswanath, Pooja Rani Mina, Prathyush Chirra, Verena Carola Obmann, Ganapati H. Mahabeleshwar, Paola Menghini, Blythe Durbin-Johnson, Jan Nolta, Christopher Soto, Abdullah Osme, Lam T. Khuat, William J. Murphy, Arnold I. Caplan, Fabio Cominelli |
| المصدر: |
npj Regenerative Medicine, Vol 9, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: |
Nature Portfolio, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Medicine |
| مصطلحات موضوعية: |
Medicine |
| الوصف: |
Abstract 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. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2057-3995 |
| Relation: |
https://doaj.org/toc/2057-3995 |
| DOI: |
10.1038/s41536-024-00347-1 |
| URL الوصول: |
https://doaj.org/article/1f75ae80e5f44a7d8febf9ed44b27251 |
| رقم الانضمام: |
edsdoj.1f75ae80e5f44a7d8febf9ed44b27251 |
| قاعدة البيانات: |
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