MSCs’ conditioned media cytokine and growth factor profiles and their impact on macrophage polarization

Abstract

Background There is a growing body of evidence that multipotent mesenchymal stromal cells’ (MSCs’) remarkable therapeutic potential is attributed not only to their differentiation and regenerative capacity, but also to the paracrine effect, underlying their immunomodulatory properties. MSCs’ secretome (i.e., cytokines, growth factors, and extracellular vesicles) is therefore increasingly discussed in the context of their ability to modulate inflammatory response and promote regeneration. There is evidence that 2D or 3D culturing conditions have an impact on the cells’ secretome, and here we aimed to compare the secretion of cytokines and growth factors in human MSCs from different sources cultured in 2D and 3D conditions and assess their effect on human macrophages polarization in vitro. Methods MSCs were derived from human adipose tissue, bone marrow, gingiva, placenta, and umbilical cord, cultured as monolayers or as cell spheroids. Their cytokine profiles were analyzed, and data standardization was carried out using a z-score. Human peripheral blood mononuclear cells-derived macrophages were then treated with umbilical cord-derived MSCs’ conditioned media and their effect on macrophages polarization was assessed. Results Our findings suggest that umbilical cord-derived MSCs’ conditioned media demonstrated the highest cytokine and growth factor levels and despite mostly pro-inflammatory cytokine profile were able to promote anti-inflammatory macrophage polarization. Conclusions Umbilical cord-derived MSCs’ conditioned media hold great potential for therapeutic use, demonstrating significant anti-inflammatory effect on human macrophages.

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients

“…However, M1 macrophages from patients with STEMI cocultured with BM-MSCs increased the expression of M2 markers (CD14, CD163 and CD206). Previous reports have indicated that macrophages polarized toward an M1 phenotype have the potential to acquire an M2 phenotype in response to the presence of IL-4 and IL-13 [38], which are secreted by MSCs [41,42]. Conversely, we demonstrate that under conditions of M2 macrophages derived from patients, BM-MSCs contribute to a greater increase in M2 markers compared to macrophages from subjects with MSCs; the results of previous reports agree with our results [24].…”

“…Furthermore, we found that cocultures of BM-MSCs with M1 or M2 macrophages derived from STEMI patients did not decrease IL-10 and IL-1Ra expression. It has been reported that macrophages previously exposed to MSCs favor the generation of Tregs [42]. The results suggest that BM-MSCs are essential in the generation of Tregs independent of the M1 or M2 microenvironment that prevails in STEMI, which contributes to the regulation of inflammation in infarction.…”

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE

“…While the secretome of MSC-EVs has shown to have high levels of IL-6 and IL-8 ( 27 ), a recent study showed that the conditioned media derived from umbilical cord (UC)-MSC promoted anti-inflammatory macrophages polarization. This despite a mostly pro-inflammatory profile of cytokines, though the authors have only investigated surface markers of M2 macrophages ( 28 ). MSC-EVs contain nucleic acids, which may bind to TLR7 and 9 as foreign nucleic acids and trigger a pro-inflammatory cascade.…”

Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent

“…In comparison with other Groups, the revealed regenerative potential of the fabricated bioequivalent might be explained by shifting a MSC expression profile as it is known, for instance, that higher amounts of MCP-1 were shown in the secretome of 3D cultures of bone marrow-derived MSC [ 64 , 65 ] and fibrin gel can stimulate the synthesis of factors by MSC (e.g., VEGF, TGF- α , and IP-10) [ 38 , 66 , 67 ], which are the key players in wound healing and enhance the reparation of the damaged epithelium and angiogenesis [ 68 ].…”