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The potential effects of stem cell‐released microvesicles (MVs) in proangiogenic therapy were explored. MVs were released from adipose‐derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells. MVs from ASCs, particularly from endothelial differentiation medium‐preconditioned ASCs, were found to have elevated levels of microRNA‐31 and to promote angiogenesis. Cell secretion is an important mechanism for stem cell‐based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell‐released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of this study was to explore the potential effects of stem cell‐released MVs in proangiogenic therapy. We observed for the first time that MVs were released from adipose‐derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Endothelial differentiation medium (EDM) preconditioning of ASCs upregulated the release of MVs and enhanced the angiogenic effect of the released MVs in vitro. RNA analysis revealed that microRNA was enriched in ASC‐released MVs and that the level of microRNA‐31 (miR‐31) in MVs was notably elevated upon EDM‐preconditioning of MV‐donor ASCs. Further studies exhibited that miR‐31 in MVs contributed to the migration and tube formation of HUVECs, microvessel outgrowth of mouse aortic rings, and vascular formation of mouse Matrigel plugs. Moreover, factor‐inhibiting HIF‐1, an antiangiogenic gene, was identified as the target of miR‐31 in HUVECs. Our findings provide the first evidence that MVs from ASCs, particularly from EDM‐preconditioned ASCs, promote angiogenesis and the delivery of miR‐31 may contribute the proangiogenic effect. Significance This study provides the evidence that microvesicles (MVs) from adipose‐derived stem cells (ASCs), particularly from endothelial differentiation medium (EDM)‐preconditioned ASCs, promote angiogenesis. An underlying mechanism of the proangiogenesis may be the delivery of microRNA‐31 via MVs from ASCs to vascular endothelial cells in which factor‐inhibiting HIF‐1 is targeted and suppressed. The study findings reveal the role of MVs in mediating ASC‐induced angiogenesis and suggest a potential MV‐based angiogenic therapy for ischemic diseases.

The extracellular matrix (ECM) is a complex assembly of macromolecules that provides both architectural support and molecular signals to cells and modulate their behaviors. Originally considered a passive mechanical structure, decades of research have since demonstrated how the ECM dynamically regulates a diverse set of cellular processes in development, homeostasis, and disease progression. In September 2021, the American Society for Matrix Biology (ASMB) organized a hybrid scientific meeting, integrating in-person and virtual formats, to discuss the latest developments in ECM research. Here, we highlight exciting scientific advances that emerged from the meeting including (1) the use of model systems for fundamental and translation ECM research, (2) ECM-targeting approaches as therapeutic modalities, (3) cell-ECM interactions, and (4) the ECM as a critical component of tissue engineering strategies. In addition, we discuss how the ASMB incorporated mentoring, career development, and diversity, equity, and inclusion initiatives in both virtual and in-person events. Finally, we reflect on the hybrid scientific conference format and how it will help the ASMB accomplish its mission moving forward.

The study described in this article evaluated surface survivability of culturable Pseudomonas aeruginosa by time and type (glass, stainless steel, and laminate) using two sampling techniques: contact plates and surface swabs. Recovery of P. aeruginosa decreased logarithmically over time and varied by surface type. P. aeruginosa survival averaged 3.75, 5.75, and 6.75 hours on laminate, glass, and stainless steel, respectively. Culturable P. aeruginosa loss on stainless steel and glass were not different (p > .05); however, laminate had significantly greater loss at each time point than either glass or stainless (p < .05). A comparison of surface swab and contact plate collection efficiencies found no significant difference for laminate surfaces. Swabs, however, had a higher collection efficiency than contact plates (p < .05). For the first time, the authors report P. aeruginosa mean survival time of 3.75-6.75 hours on clinically relevant surfaces, with P. aeruginosa on stainless steel surviving the longest. Their data also indicate that culturable surface sampling appears to most accurately represent actual P. aeruginosa surface loading when swab sampling is used.

Invadopodia are extracellular matrix (ECM) degrading structures, which promote cancer cell invasion. The nucleus is increasingly viewed as a mechanosensory organelle that determines migratory strategies. However, how the nucleus crosstalks with invadopodia is little known. Here, we report that the oncogenic septin 9 isoform 1 (SEPT9_i1) is a component of breast cancer invadopodia. SEPT9_i1 depletion diminishes invadopodia formation and the clustering of invadopodia precursor components TKS5 and cortactin. This phenotype is characterized by deformed nuclei, and nuclear envelopes with folds and grooves. We show that SEPT9_i1 localizes to the nuclear envelope and juxtanuclear invadopodia. Moreover, exogenous lamin A rescues nuclear morphology and juxtanuclear TKS5 clusters. Importantly, SEPT9_i1 is required for the amplification of juxtanuclear invadopodia, which is induced by the epidermal growth factor. We posit that nuclei of low deformability favor the formation of juxtanuclear invadopodia in a SEPT9_i1-dependent manner, which functions as a tunable mechanism for overcoming ECM impenetrability.Invadopodia are extracellular matrix (ECM) degrading structures, which promote cancer cell invasion. The nucleus is increasingly viewed as a mechanosensory organelle that determines migratory strategies. However, how the nucleus crosstalks with invadopodia is little known. Here, we report that the oncogenic septin 9 isoform 1 (SEPT9_i1) is a component of breast cancer invadopodia. SEPT9_i1 depletion diminishes invadopodia formation and the clustering of invadopodia precursor components TKS5 and cortactin. This phenotype is characterized by deformed nuclei, and nuclear envelopes with folds and grooves. We show that SEPT9_i1 localizes to the nuclear envelope and juxtanuclear invadopodia. Moreover, exogenous lamin A rescues nuclear morphology and juxtanuclear TKS5 clusters. Importantly, SEPT9_i1 is required for the amplification of juxtanuclear invadopodia, which is induced by the epidermal growth factor. We posit that nuclei of low deformability favor the formation of juxtanuclear invadopodia in a SEPT9_i1-dependent manner, which functions as a tunable mechanism for overcoming ECM impenetrability.The oncogenic SEPT9_i1 is enriched in breast cancer invadopodia in 2D and 3D ECMSEPT9_i1 promotes invadopodia precursor clustering and invadopodia elongationSEPT9_i1 localizes to the nuclear envelope and reduces nuclear deformabilitySEPT9_i1 is required for EGF-induced amplification of juxtanuclear invadopodia.HighlightsThe oncogenic SEPT9_i1 is enriched in breast cancer invadopodia in 2D and 3D ECMSEPT9_i1 promotes invadopodia precursor clustering and invadopodia elongationSEPT9_i1 localizes to the nuclear envelope and reduces nuclear deformabilitySEPT9_i1 is required for EGF-induced amplification of juxtanuclear invadopodia.Invadopodia promote the invasion of metastatic cancers. The nucleus is a mechanosensory organelle that determines migratory strategies, but how it crosstalks with invadopodia is unknown. Okletey et al show that the oncogenic isoform SEPT9_i1 promotes nuclear envelope stability and the formation of invadopodia at juxtanuclear areas of the plasma membrane.eTOC BlurbInvadopodia promote the invasion of metastatic cancers. The nucleus is a mechanosensory organelle that determines migratory strategies, but how it crosstalks with invadopodia is unknown. Okletey et al show that the oncogenic isoform SEPT9_i1 promotes nuclear envelope stability and the formation of invadopodia at juxtanuclear areas of the plasma membrane.

Cytoplasmic pressure, generated by water flow across the plasma membrane and actomyosin contractility can drive cell dynamics, including cell morphology, protrusion identity, and mode of migration. Recently, it has been discovered that mesenchymal cells migrating in highly cross-linked three-dimensional (3D) matrices regulate their intracellular pressure to achieve migratory plasticity switching from low pressure lamellipodial protrusions to high pressure lobopodial protrusions. However, the ability of cells to sense and integrate mechanical cues from the extracellular matrix for intracellular pressure generation remains unknown. Migratory plasticity can also be achieved when epithelial cells transition to mesenchymal cells through a process known as epithelial-mesenchymal transition. Yet, it remains unclear the role of intracellular pressure during this process. In the first part of my thesis, I investigated the molecular mechanism of migratory plasticity during 3D migration when activating the nuclear piston mechanism. I found that during activation of the nuclear piston there is a significant increase in nuclear mechanical stress as measured by nuclear deformation and pressure. Yet, it is not sufficient to activate the piston. However, phospho-proteomics analysis identified a potential molecular regulatory mechanism for nuclear piston activation through the Ras-MAPK signaling pathway. Upon modulation of ERK1/2 activity in primary fibroblasts migrating in 3D, I found that ERK1/2 acts as a negative regulator of the piston mechanism by suppressing intracellular pressure though non-muscle myosin II (NMII) activity in normal and aberrant cells. Critically, I found that upon piston activation by protease inhibition, endogenous ERK1/2 activity is downregulated, suggesting ERK1/2 activity is downstream of proteases. Finally, I show that Ras transformed fibroblasts promote lamellipodial migration indicating the Ras-MAPK pathway as a potential molecular switch for migratory plasticity. In the second part of my dissertation, I investigated the role of intracellular pressure in epithelial cells. I found that epithelial cells maintain a significantly higher intracellular pressure than that of mesenchymal cells on two-dimensional surfaces. This high intracellular pressure functions to maintain tissue integrity and promote barrier function. Furthermore, I show that the induction of epithelial to mesenchymal transition by hepatocyte growth factor requires intracellular pressure to decrease. This allows for the formation of lamellipodial protrusions through the actin nucleating protein, Arp2/3. Thus, reduction in cytoplasmic pressure facilitates lamellipodia formation and motility. Collectively, these data reveal the unique mechanism and role of intracellular pressure generation during 2D and 3D migration of both mesenchymal and epithelial cells. Intracellular pressure regulation functions to dynamically alter cellular migration and provides insights into the mechanism of migratory plasticity in 3D matrices.

The study described in this article evaluated surface survivability of culturablePseudomonas aeruginosaby time and type (glass, stainless steel, and laminate) using two sampling techniques: contact plates and surface swabs. Recovery ofP. aeruginosadecreased logarithmically over time and varied by surface type.P. aeruginosasurvival averaged 3.75, 5.75, and 6.75 hours on laminate, glass, and stainless steel, respectively. CulturableP. aeruginosaloss on stainless steel and glass were not different (p> .05); however, laminate had significantly greater loss at each time point than either glass or stainless (p< .05). A comparison of surface swab and contact plate collection efficiencies found no significant difference for laminate surfaces. Swabs, however, had a higher collection efficiency than contact plates (p< .05). For the first time, the authors reportP. aeruginosamean survival time of 3.75–6.75 hours on clinically relevant surfaces, withP. aeruginosaon stainless steel surviving the longest. Their data also indicate that culturable surface sampling appears to most accurately represent actualP. aeruginosasurface loading when swab sampling is used.

The study described in this article evaluated surface survivability of culturable Pseudomonas aeruginosa by time and type (glass, stainless steel, and laminate) using two sampling techniques: contact plates and surface swabs. Recovery of P. aeruginosa decreased logarithmically over time and varied by surface type. P. aeruginosa survival averaged 3.75, 5.75, and 6.75 hours on laminate, glass, and stainless steel, respectively. Culturable P. aeruginosa loss on stainless steel and glass were not different (p > .05); however, laminate had significantly greater loss at each time point than either glass or stainless (p < .05). A comparison of surface swab and contact plate collection efficiencies found no significant difference for laminate surfaces. Swabs, however, had a higher collection efficiency than contact plates (p < .05).

The study described in this article evaluated surface survivability of culturable Pseudomonas aeruginosa by time and type (glass, stainless steel, and laminate) using two sampling techniques: contact plates and surface swabs. Recovery of P. aeruginosa decreased logarithmically over time and varied by surface type. P. aeruginosa survival averaged 3.75, 5.75, and 6.75 hours on laminate, glass, and stainless steel, respectively. Culturable P. aeruginosa loss on stainless steel and glass were not different (p > .05); however, laminate had significantly greater loss at each time point than either glass or stainless (p < .05). A comparison of surface swab and contact plate collection efficiencies found no significant difference for laminate surfaces. Swabs, however, had a higher collection efficiency than contact plates (p < .05).

The study described in this article evaluated surface survivability of culturable Pseudomonas aeruginosa by time and type (glass, stainless steel, and laminate) using two sampling techniques: contact plates and surface swabs. Recovery of P. aeruginosa decreased logarithmically over time and varied by surface type. P. aeruginosa survival averaged 3.75, 5.75, and 6.75 hours on laminate, glass, and stainless steel, respectively. Culturable P. aeruginosa loss on stainless steel and glass were not different (p > .05); however, laminate had significantly greater loss at each time point than either glass or stainless (p < .05). A comparison of surface swab and contact plate collection efficiencies found no significant difference for laminate surfaces. Swabs, however, had a higher collection efficiency than contact plates (p < .05).

Cytoplasmic pressure, a function of actomyosin contractility and water flow, can regulate cellular morphology and dynamics. In mesenchymal cells, cytoplasmic pressure powers cell protrusion through physiological three-dimensional extracellular matrices. However, the role of intracellular pressure in epithelial cells is relatively unclear. Here we find that high cytoplasmic pressure is necessary to maintain barrier function, one of the hallmarks of epithelial homeostasis. Further, our data show that decreased cytoplasmic pressure facilitates lamellipodia formation during the epithelial to mesenchymal transition (EMT). Critically, activation of the actin nucleating protein Arp2/3 is required for the reduction in cytoplasmic pressure and lamellipodia formation in response to treatment with hepatocyte growth factor (HGF) to induce EMT. Thus, elevated cytoplasmic pressure functions to maintain epithelial tissue integrity, while reduced cytoplasmic pressure triggers lamellipodia formation and motility during HGF-dependent EMT.