• Acute myeloblastic leukemia
• Apoptosis
• Autophagy
• Mesenchymal stem cells

• Humans
• Apoptosis
• Umbilical Cord
• Leukemia, Myeloid, Acute/therapy
• Autophagy
• Mesenchymal Stem Cells

• Acute lymphoblastic leukemia
• Apoptosis
• Bone marrow mesenchymal stem cells
• Extracellular vesicles
• GDF15
• MAPK pathway
• Proliferation
• miR-29b-3p

• Humans
• Apoptosis/genetics
• Bone Marrow Cells
• Cell Proliferation
• Extracellular Vesicles
• Growth Differentiation Factor 15/genetics
• MicroRNAs/genetics
• Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
• Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy

Mitochondria are important organelles involved in several key cellular processes including energy production and cell death regulation. For this reason, it is unsurprising that mitochondrial function and structure are altered in several pathological states including cancer. Cancer cells present variate strategies to generate sufficient energy to sustain their high proliferation rates. These adaptative strategies can be mediated by extracellular signals such as extracellular vesicles. These vesicles can alter recipient cellular behavior by delivering their molecular cargo. This review explores the different EV-mediated mitochondrial reprogramming mechanisms supporting cancer survival and progression.

Altered metabolism is a defining hallmark of cancer. Metabolic adaptations are often linked to a reprogramming of the mitochondria due to the importance of these organelles in energy production and biosynthesis. Cancer cells present heterogeneous metabolic phenotypes that can be modulated by signals originating from the tumor microenvironment. Extracellular vesicles (EVs) are recognized as key players in intercellular communications and mediate many of the hallmarks of cancer via the delivery of their diverse biological cargo molecules. Firstly, this review introduces the most characteristic changes that the EV-biogenesis machinery and mitochondria undergo in the context of cancer. Then, it focuses on the EV-driven processes which alter mitochondrial structure, composition, and function to provide a survival advantage to cancer cells in the context of the hallmarks of cancers, such as altered metabolic strategies, migration and invasiveness, immune surveillance escape, and evasion of apoptosis. Finally, it explores the as yet untapped potential of targeting mitochondria using EVs as delivery vectors as a promising cancer therapeutic strategy.

• Differentiation
• Disease modelling
• Drug screening
• Human pluripotent stem cells
• Mesenchymal stem cells
• Regenerative medicine

Mesenchymal stem cells (MSCs) have been proposed to have potential for tissue engineering and cell therapy due to their multilineage differentiation potential and ability to secrete numerous paracrine factors, including extracellular vesicles (EVs). Increasing evidence has demonstrated that MSC‐derived EVs (MSC‐EVs) are able to induce the repair of tissue damage and regulate the immune system. However, their role in cancer development is still unclear. Reports have suggested that whether MSC‐EVs have an inhibitory or promoting effect on cancer is dependent on the type of cancer. In this study, the role of MSC‐EVs in the regulation of leukemic cell growth in vitro was investigated. The EVs were collected from conditioned media of MSCs by ultrafiltration using a 10 kDa molecular weight cutoff (MWCO) filter. The isolated MSC‐EVs were comprised of microvesicles and exosomes, as examined by the size of vesicles and exosomal proteins, CD81 and flotillin‐1. Cell proliferation, cell cycle status, apoptosis, and gene expression were examined in the leukemic cell lines NB4 and K562 after treatment with MSC‐EVs. Suppression of cell proliferation and induction of apoptosis was observed. Gene expression analysis revealed differential expression of apoptotic‐related genes in NB4 and K562. MSC‐EVs increased the expression of BID and BAX and decreased expression of BCL2, indicating the induction of intrinsic apoptosis in NB4. In contrast, MSC‐EVs increased the expression of the death receptor gene TRAILR2 and cell cycle regulator genes P21 and CCNE2 in K562. In conclusion, MSC‐EVs partially induce leukemic cell apoptosis, and thus may have potential for the development of supportive therapies for leukemia.

• exosome
• extracellular vesicle
• leukemia
• mesenchymal stem cells (MSCs)
• microvesicle

Osseointegration is the premise of the chewing function of dental implant. Nerve growth factor (NGF), as a neurotrophic factor, can induce bone healing. However, the influence of NGF-chondroitin sulfate (CS)/hydroxyapatite (HA)-coating composite implant on the osseointegration and innervations is still not entirely clear.

NGF-CS/HA-coating composite implants were prepared using the modified biomimetic method. The characteristics of NGF-CS/HA-coating implants were determined using a scanning electron microscope. After NGF-CS/HA-coating implants were placed in the mandible of Beagle dogs, the early osseointegration and innervation in peri-implant tissues were assessed through X-ray, Micro-CT, maximal pull-out force, double fluorescence staining, toluidine blue staining, DiI neural tracer, immunohistochemistry, and RT-qPCR assays.

NGF-CS/HA-coating composite implants were made successfully, which presented porous mesh structures with the main components (Ti and HA). Besides, we revealed that implantation of NGF-CS/HA-coating implants significantly changed the morphology of bone tissues and elevated maximum output, MAR, BIC, and nerve fiber in the mandible of Beagle dogs. Moreover, we proved that the implantation of NGF-CS/HA-coating implants also markedly upregulated the levels of NGF, osteogenesis differentiation, and neurogenic differentiation-related genes in the mandible of Beagle dogs.

Implantation of NGF-CS/HA-coating composite implants has significant induction effects on the early osseointegration and nerve regeneration of peri-implant tissues in the mandible of Beagle dogs.

The online version contains supplementary material available at 10.1186/s13018-020-02177-5.

• Bone marrow mesenchymal stem cells
• NGF-CS/HA-coating composite titanium
• Neuronal differentiation
• Osteogenesis differentiation

• MSCs manipulation
• Mesenchymal stem cells
• Neurodegenerative diseases

• Apoptosis
• Cell death pathway
• Ferroptosis
• Ischemic stroke
• Necroptosis
• Pyroptosis

Myocardial reperfusion injury (MRI) induced by cardiomyocyte apoptosis plays an important role in the pathogenesis of a variety of cardiovascular diseases. New MRI treatments involving stem cells are currently being developed because these cells may exert their therapeutic effects primarily through paracrine mechanisms. Microvesicles (MVs) are small extracellular vesicles that have become the key mediators of intercellular communication. MVs derived from stem cells have been reported to play an important role in MRI. In this article, we attempted to explore the mechanisms by which MVs derived from human embryonic neural stem cells (hESC-NSC-derived MVs) rescue MRI. hESCs were differentiated into NSCs, and MVs were isolated from their supernatants by ultracentrifugation. H₂O₂ was used to induce apoptosis in HL-1 cardiomyocytes. Cell viability was detected by using the CCK-8 assay, apoptosis was detected by Annexin V-FITC/PI staining, and apoptosis-related proteins and signalling pathway-related proteins were detected by western blot analysis. Autophagic flux was measured using the tandem fluorescent mRFG-GFP-LC3 assay. Transmission electron microscopy and western blot analysis were adopted to evaluate autophagy levels. hESC-NSC-derived MVs increased the autophagy and inhibited the apoptosis of HL-1 cells exposed to H₂O₂ for 3 h in a dose-dependent manner. Additionally, hESC-NSC-derived MVs contained high levels of heat shock protein 70 (HSP-70), which can increase the level of HSP-70 in cells. Moreover, the same effect could be achieved by heat shock preconditioning of HL-1 cells overexpressing HSP-70. The benefits of NSC-MVs may be due to the involvement of AKT and mTOR signalling pathways. Importantly, hESC-NSC-derived MVs stimulated the activation of the AKTand mTOR signalling pathway in those cells by transporting HSP-70. Our results suggest that hESC-NSC-derived MVs inhibit the apoptosis of HL-1 cardiomyocytes by promoting autophagy and regulating AKT and mTOR via transporting HSP-70. However, this hypothesis requires in vivo confirmation.

Cell‐derived microvesicles are membrane vesicles produced by the outward budding of the plasma membrane and released by almost all types of cells. These have been considered as another mechanism of intercellular communication, because they carry active molecules, such as proteins, lipids and nucleic acids. Furthermore, these are present in circulating fluids, such as blood and urine, and are closely correlated to the progression of pathophysiological conditions in many diseases. Recent studies have revealed that microvesicles have a dual effect of damage and protection of receptor cells. However, the nature of the active molecules involved in this effect remains unclear. The present study mainly emphasized the mechanism of microvesicles and the active molecules mediating the different biological effects of receptor cells by affecting autophagy, apoptosis and inflammation pathways. The effective ways of blocking microvesicles and its active molecules in mediating cell damage when microvesicles exert harmful effects were also discussed.

• active molecules
• apoptosis
• autophagy
• inflammation
• lipids
• miRNA
• microvesicles
• proteins

Hypoxia, as one of the severe cellular stresses, can cause cellular injury and even cell death. Apoptosis is the main mechanism of regulating cell death and is closely related to the cell death caused by hypoxia. However, hypoxia-induced apoptosis is not entirely the result of direct hypoxic stimulus of cells. In recent years, it has been found that cells injured by hypoxia can shed a kind of membranous vesicles, which are called microvesicles (MVs). MVs can carry bioactive molecules from injured mother cells and appear in blood, cerebrospinal fluid, and other body fluids. MVs can induce normal cell apoptosis by transferring bioactive molecules into adjacent cells and amplifying the hypoxic injury in an organism. This review summarizes the characteristic changes of MVs derived from hypoxic cells and the mechanism of normal cell apoptosis mediated by hypoxic cell-derived MVs. Finally, we introduce the significance of this apoptosis-apoptosis cascade reaction in hypoxic diseases.