The immune plasticity of mesenchymal stromal cells from mice and men: concordances and discrepancies
Raphaelle Romieu-Mourez1, Daniel L.Coutu1, Jacques Galipeau2
1
The Montreal Center for Experimental Therapeutics in Cancer, Jewish General Hospital, McGill University, Montreal, Quebec, Canada, 2Winship Cancer Institute of Emory University, Department of Hematology/Oncology and Pediatrics, Atlanta, GA
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. Human versus mouse MSCs: isolation and comparison with fibroblasts
- 3.1. Isolation of human MSCs
- 3.2. Isolation of mouse MSCs
- 3.3. Comparison of MSCs and fibroblasts
- 4. Immune profile of naïve human and mouse MSCs
- 4.1. Expression of molecules involved in antigen presentation
- 4.2. Expression of chemokines, cytokines, and prostaglandin E2
- 4.3. Other immune molecules expressed by MSCs
- 4.4. In vivo effects of MSCs in the absence of an ongoing immune or inflammatory response
- 5. Licensing of MSCs by inflammatory signals
- 5.1. Chemoattraction and adhesion to immune cells
- 5.2. Antigen processing
- 5.3. Immunosuppression
- 6. Immunosuppressive molecules produced by immune reaction-licensed MSCs : species differences or variations with methodology?
- 6.1. Characteristics of MSCs and immune cell co-cultures
- 6.2. PGE2 is upregulated by IFN-g and/or TNF-a in human and mouse MSCs
- 6.3. Nitric oxide versus indoleamine 2,3-dioxygenase production by mouse and human MSCs
- 6.4. Other immune suppressive factors induced by IFN-g and/or TNF-a in MSCs
- 7. Comparing human and mouse MSCs efficacy in GVHD clinical trials and mouse models
- 7.1. MSC-based GVHD clinical trials
- 7.2. Efficacy of MSCs in mouse models of GVHD
- 8. From mouse models to human studies: MSC effects in rheumatoid arthritis?
9. Summary
10. Acknowledgments
- 11. References
1. ABSTRACT
During the last decade, mesenchymal stromal cells (MSCs) have generated numbers of clinical trials to address inflammatory diseases such as GVHD, Crohn's disease and lupus. Animal models and therapeutic protocols in patients have demonstrated their anti-inflammatory and immunosuppressive properties towards adaptive immune cells. However, the basis of their immune suppression remains hotly debated. In the present review, we discuss the comparative isolation of human and rodent MSCs, their respective immune properties, whether constitutive or licensed by inflammatory or immune reactions, as well as differential efficacy as observed in GVHD clinical trials and related mouse models. Rodent MSCs display a number of immune differences with human MSCs regarding to ease of isolation, licensing pathways resulting in immunosuppression, and expression of immune mediators. These observations urge for caution when translating results generated in murine models into clinical settings.