Mesenchymal stem cells are mobilized from the bone marrow during inflammation

Area of Science:

• Immunology
• Stem Cell Biology
• Neuroimmunology

Background:

• Mesenchymal stem cells (MSCs) are promising for immune-mediated diseases like Multiple Sclerosis (MS).
• Systemic MSC administration reduces immune cell infiltration in the EAE model of MS.
• The role of endogenous MSC mobilization in disease remains unclear.

Purpose of the Study:

• To investigate the mobilization of endogenous MSCs during the acute phase of experimental allergic encephalomyelitis (EAE), an MS model.
• To determine the relationship between T cell activation and MSC numbers in the bone marrow.
• To elucidate the mechanism of MSC mobilization from bone marrow.

Main Methods:

• Monitoring bone marrow MSC numbers during the acute and progressive phases of EAE.
• Correlating MSC counts with CD4 and CD8 T cell populations in the bone marrow.
• Analyzing MSC levels in CD70-transgenic mice with activated immune systems.
• Investigating the effect of CD27-activated T cell transfer on MSC numbers, assessing IFN-γ dependency.

Main Results:

• Bone marrow MSC numbers significantly decreased during the acute phase of EAE, returning to normal levels during progression.
• A negative correlation was observed between bone marrow MSC counts and both CD4 and CD8 T cells.
• CD70-transgenic mice exhibited markedly reduced bone marrow MSCs.
• Transfer of activated T cells reduced bone marrow MSCs in an IFN-γ-dependent manner.

Conclusions:

• Endogenous MSCs are mobilized from bone marrow during immune-mediated diseases like EAE.
• Activated T cells, particularly via IFN-γ signaling, drive MSC mobilization.
• This mobilization provides a potential mechanism for MSCs to contribute to tissue repair at distant sites.