Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression.

Introduction: The tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression. Methods: Using in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussion: Neutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1ß, and IL-10 are associated with poor outcomes in patients with GB. Conclusion: These results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.

The Impact of Mesenchymal Stromal Cells on Neutrophils: A Concise Review.

This review describes the current state of knowledge concerning interactions between mesenchymal stromal cells (MSCs) and neutrophils. MSCs are known as somatic multipotent cells with regenerative and anti-inflammatory abilities and immunomodulatory effects over other immune cells. Several studies reported that MSCs could affect the function and viability of neutrophils in their recruitment, activation, activity, survival, production of reactive oxygen species, phagocytosis capacity, and apoptosis. Moreover, neutrophils could be involved in the pro-metastatic effects of MSCs. Inversally, only a few studies pointed to the possibility of the opposite effect of neutrophils on MSCs. Understanding the interactions between MSCs and neutrophils could help promote therapeutic strategies using stromal cell-based therapeutic approaches, especially for hyper-immune pathologies, immunodeficiencies, and infectious diseases. However, further in vitro and in vivo studies are essential to determine the complete mechanisms of MSCs and neutrophils interaction.

Effects of cell concentration, time of fresh storage, and cryopreservation on peripheral blood stem cells: PBSC fresh storage and cryopreservation.

INTRODUCTION: Peripheral blood stem cells are widely used in autologous or allogeneic transplantation. The quality of the product directly impacts clinical outcomes, and the cell quality and/or functionality may be influenced by the storage conditions as time, temperature, total nucleated cells (TNC) concentration and cryopreservation requirement. OBJECTIVE: To verify the effects of time, cell concentration, and cryopreservation/thawing in the viability and functionality of stem cells for transplantation. METHODS: We evaluated TNC, CD45+ viable cells, CD34+ viable cells, and cell viability and functionality of 11 samples. Measurements were performed immediately and 24 h, 48 h, 72 h, and 96 h after sample collection at high and low TNC concentrations. The same parameters were also evaluated after cryopreservation and thawing of the samples. RESULT: Duration of storage and TNC concentration exhibited a negative effect on cell quality (CD45+ viable cells, CD34+ viable cells and functionality). Moreover, the association of these parameters increased the negative effect on graft quality. Cryopreservation and thawing also negatively affected the collected sample regarding viable CD34+ cells (recovery 66.2 %), viable CD45+ cells (recovery 56.8 %), and 7-AAD viability. No significant losses in viable CD45+/CD34+ cells and functionality were observed in the first 24 h in both TNC conditions. CONCLUSION: These results emphasize the importance to consider carefully the storage conditions until transplantation, measuring TNC/µL until 24 h after collection (diluting the product when TNC > 300 × 103/µL) and infusing fresh graft as soon as possible.