Elliptical supra-cellular topographies regulate stem cells migratory pattern and osteogenic differentiation

In living systems, the extracellular environment is structured in a hierarchal order assembling into tissues in a myriad of shapes and complex geometries. Residing within the extracellular matrix, cells are presented and influenced by geometrical cues at several scales. While there is an emerging body of evidence that substrate with symmetric supra-cellular scale geometries (e.g. cylinders and spheres) influence the cell behavior, the effect of physiologically relevant, non-symmetric geometries with varying mean curvatures remain unexplored. In this study, we systematically explore the migratory and differentiation behavior of adipose derived stem cells (ADSCs) on arrays of elliptical cylinders (up to 80 × cell size) with varying mean curvature made from hydroxyapatite. Here, we report a new substrate-driven cell response, which we term “ridge-effect” that leads to osteogenic differentiation and nuclear deformation of cells adhered on regions of highest mean curvature at the ridge of the elliptical cylinders. This phenomenon is observed in both expansion and osteogenic medium. Live imaging combined with functional analysis shows that cells travel along-side the zero mean curvature direction on elliptical cylinders and significantly promote expression of collagen I and osteocalcin compared to a flat surface, in the absence of osteogenic supplements. Altogether, this work identifies supra-cellular scale topographies, and suggest the “ridge-effect” as a physical cue for guiding cellular mechanoresponse and promoting osteogenic differentiation. This knowledge could be utilized as an important biomaterial design parameter for the development of biomedical interfaces and bone scaffolds in tissue engineering and regenerative medicine

Hippo pathway effectors control cardiac progenitor cell fate by acting as dynamic sensors of substrate mechanics and nanostructure

Stem cell responsiveness to extracellular matrix (ECM) composition and mechanical cues has been the subject of a number of investigations so far, yet the molecular mechanisms underlying stem cell mechano-biology still need full clarification. Here we demonstrate that the paralog proteins YAP and TAZ exert a crucial role in adult cardiac progenitor cell mechano-sensing and fate decision. Cardiac progenitors respond to dynamic modifications in substrate rigidity and nanopattern by promptly changing YAP/TAZ intracellular localization. We identify a novel activity of YAP and TAZ in the regulation of tubulogenesis in 3D environments and highlight a role for YAP/TAZ in cardiac progenitor proliferation and differentiation. Furthermore, we show that YAP/TAZ expression is triggered in the heart cells located at the infarct border zone. Our results suggest a fundamental role for the YAP/TAZ axis in the response of resident progenitor cells to the modifications in microenvironment nanostructure and mechanics, thereby contributing to the maintenance of myocardial homeostasis in the adult heart. These proteins are indicated as potential targets to control cardiac progenitor cell fate by materials design

Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells

Gastrulation is a stage in embryo development where three germ layers arise to dictate the human body plan. In vitro models of gastrulation have been demonstrated by treating pluripotent stem cells with soluble morphogens to trigger differentiation. However, in vivo gastrulation is a multistage process coordinated through feedback between soluble gradients and biophysical forces, with the multipotent epiblast transforming to the primitive streak followed by germ layer segregation. Here, the authors show how constraining pluripotent stem cells to hydrogel islands triggers morphogenesis that mirrors the stages preceding in vivo gastrulation, without the need for exogenous supplements. Within hours of initial seeding, cells display a contractile phenotype at the boundary, which leads to enhanced proliferation, yes-associated protein (YAP) translocation, epithelial to mesenchymal transition, and emergence of SRY-box transcription factor 17 (SOX17)+ T/BRACHYURY+ cells. Molecular profiling and pathway analysis reveals a role for mechanotransduction-coupled wingless-type (WNT) signaling in orchestrating differentiation, which bears similarities to processes observed in whole organism models of development. After two days, the colonies form multilayered aggregates, which can be removed for further growth and differentiation. This approach demonstrates how materials alone can initiate gastrulation, thereby providing in vitro models of development and a tool to support organoid bioengineering efforts.Pallavi Srivastava, Sara Romanazzo, Chantal Kopecky, Stephanie Nemec, Jake Ireland, Thomas G. Molley, Kang Lin, Pavithra B. Jayathilaka, Elvis Pandzic, Avani Yeola, Vashe Chandrakanthan, John Pimanda, and Kristopher Kilia

Anxiety in the Medically Ill: A Systematic Review of the Literature

BACKGROUND: Although anxiety is highly represented in the medically ill and its occurrence has relevant clinical implications, it often remains undetected and not properly treated. This systematic review aimed to report on anxiety, either symptom or disorder, in patients who suffer from a medical illness. METHODS: English-language papers reporting on anxiety in medically ill adults were evaluated. PubMed, PsycINFO, Web of Science, and Cochrane databases were systematically searched from inception to June 2021. Search term was “anxiety” combined using the Boolean “AND” operator with “medically ill/chronic illness/illness/disorder/disease.” Risk of bias was assessed via the Joanna Briggs Institute (JBI) Critical Appraisal Tools—Checklist for Prevalence Studies. The PRISMA guidelines were followed. RESULTS: Of 100,848 citations reviewed, 329 studies met inclusion criteria. Moderate or severe anxious symptoms were common among patients with cardiovascular, respiratory, central nervous system, gastrointestinal, genitourinary, endocrine, musculoskeletal system or connective tissue, dermatological diseases, cancer, AIDS and COVID-19 infections. The most common anxiety disorder was generalized anxiety disorder, observed among patients with cardiovascular, respiratory, central nervous system, dermatologic diseases, cancer, primary aldosteronism, amenorrhea, and COVID-19 infection. Panic disorder was described for cardiovascular, respiratory, dermatology diseases. Social anxiety was found for cardiovascular, respiratory, rheumatoid diseases. Specific phobias were relatively common in irritable bowel syndrome, gastroesophageal reflux, end-stage renal disease. CONCLUSION: Anxiety is a major challenge in medical settings. Recognition and proper assessment of anxiety in patients who suffer from a medical illness is necessary for an appropriate management. Future reviews are warranted in order also to clarify the causal and temporal relationship between anxiety and organic illness

Clinimetric properties of the diagnostic criteria for psychosomatic research among the elderly

IntroductionAmong the elderly, the availability of tool assessing psychosomatic syndromes is limited. The present study aims at testing inter-rater reliability and concurrent validity of the semi-structured interview for the Diagnostic Criteria for Psychosomatic Research (DCPR-R-SSI) in the elderly of the general population. MethodOne hundred eight subjects were recruited. Participants received a clinical assessment which included the DCPR-R-SSI, the Illness Attitude Scale (IAS), the Geriatric Depression Scale (GDS), the Psychosocial Index (PSI), the Toronto Alexithymia Scale-20 (TAS-20). Analyses of inter-rater reliability of DCPR-R-SSI and concurrent validity between DCPR-R-SSI and self-administered questionnaires were conducted. ResultsDCPR-R-SSI showed excellent inter-rater reliability with a percent of agreement of 90.7% (K Cohen: 0.856 [SE = 0.043], 95% CI: 0.77-0.94). DCPR-R demoralization showed fair concurrent validity with GDS; concurrent validity was also fair between DCPR-R Alexithymia and TAS-20, and between DCPR-R allostatic overload and PSI allostatic load, while the concurrent validity between DCPR-R Disease Phobia and IAS was moderate. ConclusionDCPR-R-SSI represents a reliable and valid tool to assess psychosomatic syndromes in the elderly. DCPR-R is in need of being implemented in the elderly clinical evaluation

Targeting cell plasticity for regeneration: From in vitro to in vivo reprogramming

The discovery of induced pluripotent stem cells (iPSCs), reprogrammed to pluripotency from somatic cells, has transformed the landscape of regenerative medicine, disease modelling and drug discovery pipelines. Since the first generation of iPSCs in 2006, there has been enormous effort to develop new methods that increase reprogramming efficiency, and obviate the need for viral vectors. In parallel to this, the promise of in vivo reprogramming to convert cells into a desired cell type to repair damage in the body, constitutes a new paradigm in approaches for tissue regeneration. This review article explores the current state of reprogramming techniques for iPSC generation with a specific focus on alternative methods that use biophysical and biochemical stimuli to reduce or eliminate exogenous factors, thereby overcoming the epigenetic barrier towards vector-free approaches with improved clinical viability. We then focus on application of iPSC for therapeutic approaches, by giving an overview of ongoing clinical trials using iPSCs for a variety of health conditions and discuss future scope for using materials and reagents to reprogram cells in the body

Mental Pain Questionnaire:An item response theory analysis

Background: The Mental Pain Questionnaire (MPQ) is a self-report questionnaire developed to assess mental pain. The aim of the present study was to test the clinimetric properties of the MPQ. Methods: A sample of 200 migraine outpatients were enrolled; homogeneity of MPQ was assessed by Mokken Analysis; item-level severity and item-level sensitivity were calculated via Two-Parameter Logistic model; Total Information Function was evaluated to assess reliability of MPQ; internal consistency was calculated via Cronbach's alpha and Sijtsma and Molenaar rho; sensitivity and specificity were assessed via Receiver Operating Characteristic curves. Results: The MPQ showed unidimensional factor structure; satisfactory homogeneity of the item and total score, except items 4 ("my pain is everywhere") and 6 ("I cannot understand why I feel this pain"); good discrimination, except item 7 ("I feel empty"); low information provided by items 4, 6, 7; good reliability for mild and high levels of mental pain; poor reliability for low levels of mental pain; acceptable internal consistency; acceptable sensitivity and specificity. Limitations: The sample size is barely sufficient to calculate item parameters; it is a monocentric study that enrolled outpatients from a tertiary facility; the study enrolled migraine outpatients not affected by other medical disease. Conclusions: The MPQ showed good psychometric properties. Items 4, 6, 7 should be considered with caution when migraine patients are evaluated. A score of at least 3 indicates mental pain clinically relevant, a score of at least 2 indicates distress. These data are preliminary and refer to migraine patients, results might be different in psychiatric populations

A new take on the food system distribution and purchase

Sustainability is a theme often argued by many but practically handled by few. Nowadays, the environmental debate is more and more felt on every level of the social hierarchy and persistently pushed by continuous government regulations. From companies’ point of view, deciding to define sustainable behaviours as fundamental requirements of one’s production chain is a duty rather than a strategic choice. There are, however, countless ways to innovate in the field of sustainability, some more well- known and praised than others; if one were to consider the food conservation industry and take into account the behaviour of companies involved in such field, for instance, one would soon realize how little is done to find innovative ways to tackle the environmental crisis, as well as transmit to the consumers values such as freshness and quality. The University-Industry synergy was at the base of this research and made it possible to observe and study the industrial reality from a fresh perspective. The thorough corporate know-how, the deep data and context analysis carried out during the initial phases of the project and the continuous dialogue and feedback from the company inner elements made it possible to develop a refrigeration system which rethinks entirely the current refrigeration methods put in place by the main companies and takes a new direction towards a more sustainable way of displaying, purchasing and distributing food in grocerant environments. This is made possible through the localized distribution of cold, which allows food to be stored and distributed without the use of packaging and with more thorough and individual control on temperatures, in order to optimize its organoleptic qualities and extend its life span. The University-Industry cooperation also allowed to better understand inner company dynamics and generate innovative thinking, such as involving the final client in the ideation process in order to increase awareness over the sustainability of food conservation products and the value of the products themselves. This research aims at finding innovative solutions to increase consumers’ knowledge of food quality and to involve them in the processes meant to face the environmental crisis. Transforming in a circular connection between three parties - the company, the client and the final user - a B2B relationship which previously only involved the producing company and the buying client

Synthetic Bone-Like Structures Through Omnidirectional Ceramic Bioprinting in Cell Suspensions

The integration of hierarchical structure, chemistry, and functional activity within tissue-engineered scaffolds is of great importance in mimicking native bone tissue. Bone is a highly mineralized tissue which forms at ambient conditions by continuous crystallization of the mineral phase within an organic matrix in the presence of bone residing cells. Despite recent advances in the biofabrication of complex engineered tissues, replication of the heterogeneity of bone microenvironments has been a major challenge in constructing biomimetic bone scaffolds. Herein, inspired by the bone biomineralization process, the first example of bone mimicking constructs by 3D writing of a novel apatite-transforming ink in a supportive microgel matrix with living cells is demonstrated. Using this technique, complex bone-mimicked constructs are made at room temperature without requiring invasive chemicals, radiation, or postprocessing steps. This study demonstrates that mineralized constructs can be deposited within a high density of stem cells, directing the cellular organization, and promoting osteogenesis in vitro. These findings offer a new strategy for fabrication of bone mimicking constructs for bone tissue regeneration with scope to generate custom bone microenvironments for disease modeling, multicellular delivery, and in vivo bone repair

Porous Chitosan Films Support Stem Cells and Facilitate Sutureless Tissue Repair

Photochemical tissue bonding with chitosan-based adhesive films is an experimental surgical technique that avoids the risk of thermal tissue injuries and the use of sutures to maintain strong tissue connection. This technique is advantageous over other tissue repair methods as it is minimally invasive and does not require mixing of multiple components before or during application. To expand the capability of the film to beyond just a tissue bonding device and promote tissue regeneration, in this study, we designed bioadhesive films that could also support stem cells. The films were modified with oligomeric chitosan to tune their erodibility and made porous through freeze-drying for better tissue integration. Of note, porous adhesive films (pore diameter â110 μm), with 10% of the chitosan being oligomeric, could retain similar tissue bonding strengths (13-15 kPa) to that of the nonporous chitosan-based adhesives used in previous studies when photoactivated. When tested in vitro, these films exhibited a mass loss of â20% after 7 days, swelling ratios of â270-300%, a percentage elongation of â90%, and both a tensile strength and Young's modulus of â1 MPa. The physical properties of the films were suitable for maintaining the viability and multipotency of bone-marrow-derived human mesenchymal stem cells over the duration of culture. Thus, these biocompatible, photoactivated porous, and erodible adhesive films show promise for applications in controlled cell delivery and regenerative medicine