Microgravity in space or simulated by special ground-based devices provides an unusual but unique environment to study and influence tumour cell processes. By investigating thyroid cancer cells in microgravity for nearly 20 years, researchers got insights into tumour biology that had not been possible under normal laboratory conditions: adherently growing cancer cells detach from their surface and form three-dimensional structures. The cells included in these multicellular spheroids (MCS) were not only altered but behave also differently to those grown in flat sheets in normal gravity, more closely mimicking the conditions in the human body. Therefore, MCS became an invaluable model for studying metastasis and developing new cancer treatment strategies via drug targeting. Microgravity intervenes deeply in processes such as apoptosis and in structural changes involving the cytoskeleton and the extracellular matrix, which influence cell growth. Most interestingly, follicular thyroid cancer cells grown under microgravity conditions were shifted towards a less-malignant phenotype. Results from microgravity research can be used to rethink conventional cancer research and may help to pinpoint the cellular changes that cause cancer. This in turn could lead to novel therapies that will enhance the quality of life for patients or potentially develop new preventive countermeasures.
The literature suggests morphological alterations and molecular biological changes within the cellular milieu of human cells, exposed to microgravity (µ g ), as many cell types assemble to multicellular spheroids (MCS). In this study we investigated juvenile normal human dermal fibroblasts (NHDF) grown in simulated µ g (s-µ g ) on a random positioning machine (RPM), aiming to study changes in cell morphology, cytoskeleton, extracellular matrix (ECM), focal adhesion and growth factors. On the RPM, NHDF formed an adherent monolayer and compact MCS. For the two cell populations we found a differential regulation of fibronectin, laminin, collagen-IV, aggrecan, osteopontin, TIMP-1, integrin-β 1 , caveolin-1, E-cadherin, talin-1, vimentin, α-SM actin, TGF-β 1 , IL-8, MCP-1, MMP-1, and MMP-14 both on the transcriptional and/or translational level. Immunofluorescence staining revealed only slight structural changes in cytoskeletal components. Flow cytometry showed various membrane-bound proteins with considerable variations. In silico analyses of the regulated proteins revealed an interaction network, contributing to MCS growth via signals mediated by integrin-β 1 , E-cadherin, caveolin-1 and talin-1. In conclusion, s-µ g -conditions induced changes in the cytoskeleton, ECM, focal adhesion and growth behavior of NHDF and we identified for the first time factors involved in fibroblast 3D-assembly. This new knowledge might be of importance in tissue engineering, wound healing and cancer metastasis.
The accuracy of the implant’s post-operative position and orientation in reverse shoulder arthroplasty is known to play a significant role in both clinical and functional outcomes. Whilst technologies such as navigation and robotics have demonstrated superior radiological outcomes in many fields of surgery, the impact of augmented reality (AR) assistance in the operating room is still unknown. Malposition of the glenoid component in shoulder arthroplasty is known to result in implant failure and early revision surgery. The use of AR has many promising advantages, including allowing the detailed study of patient-specific anatomy without the need for invasive procedures such as arthroscopy to interrogate the joint’s articular surface. In addition, this technology has the potential to assist surgeons intraoperatively in aiding the guidance of surgical tools. It offers the prospect of increased component placement accuracy, reduced surgical procedure time, and improved radiological and functional outcomes, without recourse to the use of large navigation or robotic instruments, with their associated high overhead costs. This feasibility study describes the surgical workflow from a standardised CT protocol, via 3D reconstruction, 3D planning, and use of a commercial AR headset, to AR-assisted k-wire placement. Post-operative outcome was measured using a high-resolution laser scanner on the patient-specific 3D printed bone. In this proof-of-concept study, the discrepancy between the planned and the achieved glenoid entry point and guide-wire orientation was approximately 3 mm with a mean angulation error of 5°.
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