Mesenchymal stem cells (MSCs) represent a heterogeneous cellular population responsible for the support, maintenance, and regulation of normal hematopoietic stem cells (HSCs). In many hematological malignancies, however, MSCs are deregulated and may create an inhibitory microenvironment able to induce the disease initiation and/or progression. MSCs secrete soluble factors including extracellular vesicles (EVs), which may influence the bone marrow (BM) microenvironment via paracrine mechanisms. MSC-derived EVs (MSC-EVs) may even mimic the effects of MSCs from which they originate. Therefore, MSC-EVs contribute to the BM homeostasis but may also display multiple roles in the induction and maintenance of abnormal hematopoiesis. Compared to MSCs, MSC-EVs have been considered a more promising tool for therapeutic purposes including the prevention and treatment of Graft Versus Host Disease (GVHD) following allogenic HSC transplantation (HSCT). There are, however, still unanswered questions such as the molecular and cellular mechanisms associated with the supportive effect of MSC-EVs, the impact of the isolation, purification, large-scale production, storage conditions, MSC source, and donor characteristics on MSC-EV biological effects as well as the optimal dose and safety for clinical usage. This review summarizes the role of MSC-EVs in normal and malignant hematopoiesis and their potential contribution in treating GVHD.

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Silver nanoparticles (AgNPs) have been demonstrated to restrain bacterial growth, while maintaining minimal risk in development of bacterial resistance and human cell toxicity that conventional silver compounds exhibit. Several physical and chemical methods have been reported to synthesize AgNPs. However, these methods are expensive and involve heavy chemical reduction agents. An alternative approach to produce AgNPs in a cost-effective and environmentally friendly way employs a biological pathway using various plant extracts to reduce metal ions. The size control issue, and the stability of nanoparticles, remain some of the latest challenges in such methods. In this study, we used two different concentrations of fresh leaf extract of the plant Arbutus unedo (LEA) as a reducing and stabilizing agent to produce two size variations of AgNPs. UV-Vis spectroscopy, Dynamic Light Scattering, Transmission Electron Microscopy, and zeta potential were applied for the characterization of AgNPs. Both AgNP variations were evaluated for their antibacterial efficacy against the gram-negative species Escherichia coli and Pseudomonas aeruginosa, as well as the gram-positive species Bacillus subtilis and Staphylococcus epidermidis. Although significant differences have been achieved in the nanoparticles’ size by varying the plant extract concentration during synthesis, the antibacterial effect was almost the same.

Chitosan/Gelatin (CS:Gel) scaffolds were fabricated by chemical crosslinking with glutaraldehyde or genipin by freeze drying. Both crosslinked CS:Gel scaffold types with a mass ratio of 40:60% form a gel-like structure with interconnected pores. Dynamic rheological measurements provided similar values for the storage modulus and the loss modulus of the CS:Gel scaffolds when crosslinked with the same concentration of glutaraldehyde vs. genipin. Compared to genipin, the glutaraldehyde-crosslinked scaffolds supported strong adhesion and infiltration of pre-osteoblasts within the pores as well as survival and proliferation of both MC3T3-E1 pre-osteoblastic cells after 7 days in culture, and human bone marrow mesenchymal stem cells (BM-MSCs) after 14 days in culture. The levels of collagen secreted into the extracellular matrix by the pre-osteoblasts cultured for 4 and 7 days on the CS:Gel scaffolds, significantly increased when compared to the tissue culture polystyrene (TCPS) control surface. Human BM-MSCs attached and infiltrated within the pores of the CS:Gel scaffolds allowing for a significant increase of the osteogenic gene expression of RUNX2, ALP, and OSC. Histological data following implantation of a CS:Gel scaffold into a mouse femur demonstrated that the scaffolds support the formation of extracellular matrix, while fibroblasts surrounding the porous scaffold produce collagen with minimal inflammatory reaction. These results show the potential of CS:Gel scaffolds to support new tissue formation and thus provide a promising strategy for bone tissue engineering.