Corrigendum: Challenge of material haemocompatibility for microfluidic blood-contacting applications.

[This corrects the article DOI: 10.3389/fbioe.2023.1249753.].

Challenge of material haemocompatibility for microfluidic blood-contacting applications.

Biological applications of microfluidics technology is beginning to expand beyond the original focus of diagnostics, analytics and organ-on-chip devices. There is a growing interest in the development of microfluidic devices for therapeutic treatments, such as extra-corporeal haemodialysis and oxygenation. However, the great potential in this area comes with great challenges. Haemocompatibility of materials has long been a concern for blood-contacting medical devices, and microfluidic devices are no exception. The small channel size, high surface area to volume ratio and dynamic conditions integral to microchannels contribute to the blood-material interactions. This review will begin by describing features of microfluidic technology with a focus on blood-contacting applications. Material haemocompatibility will be discussed in the context of interactions with blood components, from the initial absorption of plasma proteins to the activation of cells and factors, and the contribution of these interactions to the coagulation cascade and thrombogenesis. Reference will be made to the testing requirements for medical devices in contact with blood, set out by International Standards in ISO 10993-4. Finally, we will review the techniques for improving microfluidic channel haemocompatibility through material surface modifications-including bioactive and biopassive coatings-and future directions.

Increased IL-6 secretion by aged human mesenchymal stromal cells disrupts hematopoietic stem and progenitor cells' homeostasis.

Hematopoietic stem and progenitor cell (HSPC) homeostasis declines with age, leading to impaired hematopoiesis. Mesenchymal stromal cells (MSC) are critical components of the bone marrow niche and key regulators of the balance between HSPC proliferation and quiescence. Accrual of DNA damage, a hallmark of cellular aging, occurs in aged MSC. Whether MSC aging alters the bone marrow niche triggering HSPC dysfunction is unknown. Using a human MSC-HSPC co-culture system, we demonstrated that DNA damaged MSC have impaired capacity to maintain CD34+CD38- HSPC quiescence. Furthermore, human MSC from adult donors display some hallmarks of cellular senescence and have a decreased capacity to maintain HSPC quiescence and the most primitive CD34+CD38- subset compared to MSC from pediatric donors. IL-6 neutralization restores the MSC-HPSC crosstalk in senescent and adult MSC-HSPC co-cultures highlighting the relevance of the local microenvironment in maintaining HSPC homeostasis. These results provide new evidence implicating components of the MSC secretome in HSPC aging.

DDR-mediated crosstalk between DNA-damaged cells and their microenvironment.

The DNA damage response (DDR) is an evolutionarily conserved signaling cascade that senses and responds to double-strand DNA breaks by organizing downstream cellular events, ranging from appropriate DNA repair to cell cycle checkpoints. In higher organisms, the DDR prevents neoplastic transformation by directly protecting the information contained in the genome and by regulating cell fate decisions, like apoptosis and senescence, to ensure the removal of severely damaged cells. In addition to these well-studied cell-autonomous effects, emerging evidence now shows that the DDR signaling cascade can also function in a paracrine manner, thus influencing the biology of the surrounding cellular microenvironment. In this context, the DDR plays an emerging role in shaping the damaged tumor microenvironment through the regulation of tissue repair and local immune responses, thereby providing a promising avenue for novel therapeutic interventions. Additionally, while DDR-mediated extracellular signals can convey information to surrounding, undamaged cells, they can also feedback onto DNA-damaged cells to reinforce selected signaling pathways. Overall, these extracellular DDR signals can be subdivided into two time-specific waves: a rapid bystander effect occurring within a few hours of DNA damage; and a late, delayed, senescence-associated secretory phenotype generally requiring multiple days to establish. Here, we highlight and discuss examples of rapid and late DDR-mediated extracellular alarm signals.