Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages

By Jaehyup Kim, P. Hematti. Experimental Hematology, 2009

769 citations recorded by the source corpus.

Objective Mesenchymal stem cells (MSCs) are capable of modulating the immune system through interaction with a wide range of immune cells. This study investigates the hypothesis that interaction of MSCs with macrophages could play a significant role in their anti-inflammatory/immune modulatory effects. Materials and Methods MSCs were derived from bone marrow and monocytes were isolated from peripheral blood of healthy donors. We cultured human monocytes for seven days without any added cytokines to generate macrophages, and then co-cultured them for three more days with culture-expanded MSCs. We used cell surface antigen expression and intracellular cytokine expression patterns to study the immunophenotype of macrophages at the end of this co-culture period, and phagocytic assays to investigate their functional activity in vitro. Results Macrophages co-cultured with MSCs consistently showed high level expression of CD206, a marker of alternatively activated macrophages. Furthermore, these macrophages expressed high levels of IL-10 and low levels of IL-12, as determined by intracellular staining, typical of alternatively activated macrophages. However, macrophages co-cultured with MSCs also expressed high levels of IL-6 and low levels of TNF-α, compared to controls. Functionally, macrophages co-cultured with MSCs showed a higher level of phagocytic activity. Conclusions We describe a novel type of human macrophage generated in vitro after co-culture with MSCs that assume an immunophenotype defined as IL-10 high, IL-12 low, IL-6 high and TNF-α low secreting cells. These MSC-educated macrophages may be a unique and novel type of alternatively activated macrophages with potentially significant role in tissue repair.

Subfields: Genetics, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9ea48c79952095950b5e22bd195bc3a3b82b5deb

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Citations in the corpus

Macrophage plasticity and polarization in tissue repair and remodelling (2013, background): “MSCs have been reported to induce an IL-10high IL-12low alternative (M2) activation phenotype in macrophages [18].”
Inflammation, Fracture and Bone Repair (2016, background): “nomodulatory effects, promoting the alternative activation of macrophages toward the pro-remodeling M2-subset [115,188].”
Mesenchymal stem cell-macrophage crosstalk and bone healing (2018, result): “observed similar results using human peripheral blood monocytes and MSCs showing induction of an anti-inflammatory, M2-like phenotype in macrophages co-cultured with MSCs [63].”
The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes (2018, background): “MSCs have such powerful modulating effects on macrophages, that some have defined yet another phenotype of macrophages based on this interaction (Kim and Hematti, 2009).”
Mesenchymal Stromal Cells Modulate Macrophages in Clinically Relevant Lung Injury Models by Extracellular Vesicle Mitochondrial Transfer (2017, background): “This corroborates previous reports showing that MSCs are able to suppress secretion of pro-inflammatory cytokines by macrophages((40)).”
Biomaterial based modulation of macrophage polarization: A review and suggested design principles (2015, background): “, and are referred to as MSC educated macrophages (MSC-Mo) [84].”
Mesenchymal Stem Cells: Mechanisms of Immunomodulation and Homing (2010, background): “Kim and Hematti were the fi rst to observe that macrophages cultured in the presence of MSC adopted phenotypes indicative of M2 macrophages (CD206 high , IL-10 high , IL-12 low ) after 48 h of culture [ 72 ] .”
Resolution of inflammation: an integrated view (2013, positive): “Conversely, MSCs profoundly inﬂuence macrophage function by inducing a IL10 high IL12 low alternative activation phenotype (Kim & Hematti, 2009).”