Cytokine physiognomies of MSCs from varied sources confirm the regenerative commitment post‐coculture with activated neutrophils

Abstract

The interaction of mesenchymal stromal cells (MSCs) with paracrine signals and immunological cells, and their responses and regenerative commitment thereafter, is understudied. In the current investigation, we compared MSCs from the umbilical cord blood (UCB), dental pulp (DP), and liposuction material (LS) on their ability to respond to activated neutrophils. Cytokine profiling (interleukin‐1α [IL‐1α], IL‐2, IL‐4, IL‐6, IL‐8, tumor necrosis factor‐α [TNF‐α], interferon‐γ [IFN‐γ], transforming growth factor‐β [TGF‐β]), cellular proliferation and osteogenic differentiation patterns were assessed. The results showed largely comparable cytokine profiles with higher TNF‐α and IFN‐γ levels in LSMSCs owing to their mature cellular phenotype. The viability and proliferation between LS/DP/UCB MSCs were comparable in the coculture group, while direct activation of MSCs with lipopolysaccharide (LPS) showed comparable proliferation with significant cell death in UCB MSCs and slightly higher cell death in the other two types of MSC. Furthermore, when MSCs post‐neutrophil exposure were induced for osteogenic differentiation, though all the MSCs devoid of the sources differentiated, we observed rapid and significant turnover of DPMSCs positive of osteogenic markers rather than LS and UCB MSCs. We further observed a significant turnover of IL‐1α and TGF‐β at mRNA and cytokine levels, indicating the commitment of MSCs to differentiate through interacting with immunological cells or bacterial products like neutrophils or LPS, respectively. Taken together, these results suggest that MSCs have more or less similar cytokine responses devoid of their anatomical niche. They readily switch over from the cytokine responsive cell phenotype at the immunological microenvironment to differentiate and regenerate tissue in response to cellular signals.

Effects of immune cells on mesenchymal stem cells during fracture healing

“…Here, a reactive oxygen species (ROS)-dependent mechanism was proposed. This is in contrast to a recent study, showing that neutrophils alter cytokine release by MSCs but not their osteogenic differentiation[ 38 ], suggesting that the activation status of the neutrophils is critical in this process.…”

Development of an immune-related prognostic index associated with osteosarcoma

“…Immune infiltration is a feature of most cancers, and many cancers have a complex chemokine network that modulates tumor cell growth, survival and migration, as well as the extent and phenotype of this infiltration [ 26 , 27 ]. Neutrophils might play an essential role in tumor progression and development by providing a suitable microenvironment for their growth, thus serving as biomarkers for inflammation and as therapeutic targets [ 28 , 29 ]. On the other hand, tumor-associated macrophages (TAMs) promote tumor progression by providing nutrients for the invasion of tumor cells [ 30 , 31 ].…”

Mesenchymal Stem Cell–Immune Cell Interaction and Related Modulations for Bone Tissue Engineering

“…In particular, TNF- α , a member of the TNF family, can bind to tumor necrosis factor receptor 1 (TNFR1) and TNFR2 receptors and exert two main effects upon binding, namely, mediating programmed cell death via the Fas pathway and maintaining cell growth by activating the transcription factors NF- κ B, activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) [ 45 , 46 ]. In innate immune responses, activated neutrophils may induce MSCs to differentiate into osteoblasts by changing IL-1 α and TGF- β levels [ 47 ]. Some experiments have also shown that neutrophils inhibit the production of the extracellular matrix from MSCs and even induce MSC apoptosis by producing reactive oxygen species (ROS) [ 48 , 49 ].…”