Crosstalk between Mesenchymal Stem Cells and Macrophages in Tissue Repair

Tissue repair post injury is a multi-step wound healing process and consists of inflammatory, proliferative, and remodeling phases, which are coordinated by interplays between many resident and infiltrating cells as well as growth factors and extracellular matrix proteins. Macrophages are major cell populations regulating inflammation by initiation, propagation, and resolution. Activated macrophages that are differentially polarized, either classically or alternatively, are also called pro-inflammatory M1 and anti-inflammatory M2, respectively. These macrophages participate in the whole process of tissue repair. The contribution of multi-potent mesenchymal stem cells (MSCs) in tissue repair, either endogenous or therapeutically injected, has been addressed in a variety of degenerative and inflammatory disease models. Initially, the role of MSCs in the tissue repair process was restricted to the replacement of dysfunctional cells by either mesenchymal differentiation or transdifferentiation into other lineages. However, growing evidence has clearly defined MSCs as beneficial cells in tissue repair via immunomodulatory functions. In this review, we intend to summarize recent important observations in two essential cell components, MSCs and macrophages, in the context of tissue repair. Individual roles of MSCs and macrophages as well as the crosstalk between these two types of cells are discussed. The roles of both MSC-educated macrophages and macrophage-associated MSCs during tissue repair are also discussed.