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Nanoscale Sep 2023Atomic Force Microscopy (AFM) is successfully used for the quantitative investigation of the cellular mechanosensing of the microenvironment. To this purpose, several...
Atomic Force Microscopy (AFM) is successfully used for the quantitative investigation of the cellular mechanosensing of the microenvironment. To this purpose, several force spectroscopy approaches aim at measuring the adhesive forces between two living cells and also between a cell and an appropriate reproduction of the extracellular matrix (ECM), typically exploiting tips suitably functionalised with single components ( collagen, fibronectin) of the ECM. However, these probes only poorly reproduce the complexity of the native cellular microenvironment and consequently of the biological interactions. We developed a novel approach to produce AFM probes that faithfully retain the structural and biochemical complexity of the ECM; this was achieved by attaching to an AFM cantilever a micrometric slice of native decellularised ECM, which was cut by laser microdissection. We demonstrate that these probes preserve the morphological, mechanical, and chemical heterogeneity of the ECM. Native ECM probes can be used in force spectroscopy experiments aimed at targeting cell-microenvironment interactions. Here, we demonstrate the feasibility of dissecting mechanotransductive cell-ECM interactions in the 10 pN range. As proof-of-principle, we tested a rat bladder ECM probe against the AY-27 rat bladder cancer cell line. On the one hand, we obtained reproducible results using different probes derived from the same ECM regions; on the other hand, we detected differences in the adhesion patterns of distinct bladder ECM regions (submucosa, detrusor, and adventitia), in line with the disparities in composition and biophysical properties of these ECM regions. Our results demonstrate that native ECM probes, produced from patient-specific regions of organs and tissues, can be used to investigate cell-microenvironment interactions and early mechanotransductive processes by force spectroscopy. This opens new possibilities in the field of personalised medicine.
PubMed: 37700706
DOI: 10.1039/d3nr01568h -
Radiology Case Reports Dec 2023A peripheral pulmonary artery aneurysm (PAA) is a dilatation involving all 3-vessel wall layers (the intima, media, and adventitia) of a distal pulmonary artery. It...
A peripheral pulmonary artery aneurysm (PAA) is a dilatation involving all 3-vessel wall layers (the intima, media, and adventitia) of a distal pulmonary artery. It represents a rare but potentially life-threatening condition. There are only some reviews of transcatheter embolization of unruptured idiopathic peripheral PAAs. Association with cardiac diseases, infections, vascular anomalies, pulmonary hypertension, and vasculitis has been noted. We report a case of a 38-year-old woman, with a history of third-degree atrioventricular (AV) block, treated with pacemaker placement, who presented a PAA in the left pulmonary lobe. Transcatheter coil embolization was performed, using a triple coaxial catheter system (a 6F outer, a 5F intermediate, and a 2.4F inner catheter) to prevent rupture and the aneurysm was successfully embolized. Although there is no consensus on the treatment for unruptured idiopathic peripheral PAAs, transcatheter embolization may be a promising treatment option.
PubMed: 37823049
DOI: 10.1016/j.radcr.2023.09.021 -
MedRxiv : the Preprint Server For... Apr 2024Computational analysis of histopathological specimens holds promise in identifying biomarkers, elucidating disease mechanisms, and streamlining clinical diagnosis....
Computational analysis of histopathological specimens holds promise in identifying biomarkers, elucidating disease mechanisms, and streamlining clinical diagnosis. However, the application of deep learning techniques in vascular pathology remains underexplored. Here, we present a comprehensive evaluation of deep learning-based approaches to analyze digital whole-slide images of abdominal aortic aneurysm samples from 369 patients from three European centers. Deep learning demonstrated robust performance in predicting inflammatory characteristics, particularly in the adventitia, as well as fibrosis grade and remaining elastic fibers in the tunica media. Overall, this study represents the first comprehensive evaluation of computational pathology in vascular disease and has the potential to contribute to improved understanding of abdominal aortic aneurysm pathophysiology and personalization of treatment strategies, particularly when integrated with radiological phenotypes and clinical outcomes.
PubMed: 38712033
DOI: 10.1101/2024.04.23.24306178 -
Journal of Vascular Research 2024Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We...
INTRODUCTION
Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We hypothesize that perivascular adipose tissue (PVAT) is responsive to hypertension and remodels as a protective measure.
METHODS
The adventitia and PVAT of the thoracic aorta were used in measuring ECM genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% Kcal fat) or high-fat (HF; 60%) diet. A PCR array of ECM genes was performed with cDNA from adventitia and PVAT after 8 and 24 weeks. A gene regulatory network of the differentially expressed genes (DEGs) (HF 2-fold > con) was created using Cytoscape.
RESULTS
After 8 weeks, 29 adventitia but 0 PVAT DEGs were found. By contrast, at 24 weeks, PVAT possessed 47 DEGs while adventitia had 3. Top DEGs at 8 weeks in adventitia were thrombospondin 1 and collagen 8a1. At 24 weeks, thrombospondin 1 was also a top DEG in PVAT. The transcription factor Adarb1 was identified as a regulator of DEGs in 8-week adventitia and 24-week PVAT.
CONCLUSION
These data support that PVAT responds biologically once blood pressure is elevated.
Topics: Rats; Animals; Male; Diet, High-Fat; Thrombospondin 1; Blood Pressure; Rats, Inbred Dahl; Adipose Tissue; Hypertension
PubMed: 38113863
DOI: 10.1159/000535513 -
Surgical Case Reports Jun 2024The most common curative treatment for gastrointestinal stromal tumors (GISTs) is local excision. For rectal GISTs, however, local excision is difficult because of the...
BACKGROUND
The most common curative treatment for gastrointestinal stromal tumors (GISTs) is local excision. For rectal GISTs, however, local excision is difficult because of the anatomical features of the rectum. The optimal surgical approach is still under debate, and less invasive methods are desired. We herein report a case of transvaginal resection of a rectal GIST in a young woman.
CASE PRESENTATION
A 21-year-old woman was diagnosed with a resectable GIST in the anterior rectal wall and underwent transvaginal tumor resection. The posterior vaginal wall was incised, revealing the tumor fully covered by the rectal mucosa. The rectal adventitia and muscular layer were incised, and the tumor was resected en bloc without rupture. The postoperative course was favorable, and the patient was discharged on postoperative day 12. No findings consistent with recurrence were present 6 months postoperatively.
CONCLUSION
Transvaginal tumor resection is a treatment option as a minimally invasive procedure for GISTs in the anterior rectal wall in female patients.
PubMed: 38886293
DOI: 10.1186/s40792-024-01949-z -
Stem Cells Translational Medicine Jul 2023Innate mesenchymal stem cells exhibiting multilineage differentiation and tissue (re)generative-or pathogenic-properties reside in perivascular niches. Subsets of these...
Innate mesenchymal stem cells exhibiting multilineage differentiation and tissue (re)generative-or pathogenic-properties reside in perivascular niches. Subsets of these progenitors are committed to either osteo-, adipo-, or fibrogenesis, suggesting the existence of a developmental organization in blood vessel walls. We evaluated herein the activity of aldehyde dehydrogenase, a family of enzymes catalyzing the oxidation of aldehydes into carboxylic acids and a reported biomarker of normal and malignant stem cells, within human adipose tissue perivascular areas. A progression of ALDHLow to ALDHHigh CD34+ cells was identified in the tunica adventitia. Mesenchymal stem cell potential was confined to ALDHHigh cells, as assessed by proliferation and multilineage differentiation in vitro of cells sorted by flow cytometry with a fluorescent ALDH substrate. RNA sequencing confirmed and validated that ALDHHigh cells have a progenitor cell phenotype and provided evidence that the main isoform in this fraction is ALDH1A1, which was confirmed by immunohistochemistry. This demonstrates that ALDH activity, which marks hematopoietic progenitors and stem cells in diverse malignant tumors, also typifies native, blood vessel resident mesenchymal stem cells.
Topics: Humans; Aldehyde Dehydrogenase; Stem Cells; Mesenchymal Stem Cells; Cell Differentiation; Flow Cytometry
PubMed: 37261440
DOI: 10.1093/stcltm/szad024 -
Journal of Biomechanics Aug 2023So far, the prevalent rupture risk quantification of aortic aneurysms does not consider information of the underlying microscopic mechanisms. Uniaxial tension tests were...
So far, the prevalent rupture risk quantification of aortic aneurysms does not consider information of the underlying microscopic mechanisms. Uniaxial tension tests were performed on imaged aorta samples oriented in circumferential and longitudinal directions. To account for local heterogeneity in collagen fiber architecture, SHG imaging was performed on tissues at several locations prior to mechanical testing. This enabled the quantification of micro-scale information including organization of collagen fibers using relevant probability density functions. Two different modeling approaches are presented in this study for the sake of comparison. A multi-scale mechanical model was developed using this micro-structural information with collagen fibers as main components. accounting for non-affine fiber kinematics. Simultaneously, an embedded element model that accounts for affine fiber kinematics was developed in Abaqus using the same micro-structural information. Numerical simulations emulating uniaxial tension experiments were performed on the developed models. Global mechanical response of both models agreed well with the experimental data, although leading to mismatched material properties. The models present a rudimentary yet better than before representation of structure based description of aortic-tissue failure mechanics. reinforcing the importance of structural organization of micro-scale constituents and their kinematics in determining tissue failure.
Topics: Collagen; Stress, Mechanical; Arteries; Aorta; Extracellular Matrix; Biomechanical Phenomena
PubMed: 37478803
DOI: 10.1016/j.jbiomech.2023.111700 -
PloS One 2023Tissue engineering has driven significant research in the strive to create a supply of tissues for patient treatment. Cell integration into engineered tissues maximizes...
Tissue engineering has driven significant research in the strive to create a supply of tissues for patient treatment. Cell integration into engineered tissues maximizes functional capabilities, however, issues of rejection remain. Autologous cell sources able to solve this issue are difficult to identify for tissue engineering purposes. Here, we present the efficacy of patient-sourced cells derived from adipose (adipose-derived stem cells, ASCs) and skin tissue (dermal fibroblasts, PtFibs) to build a combined engineered tunica media and adventitia graft, respectively. Patient cells were integrated into our lab's vascular tissue engineering technique of forming vascular rings that are stacked into a tubular structure to create the vascular graft. For the media layer, ASCs were successfully differentiated into the smooth muscle phenotype using angiotensin II followed by culture in smooth muscle growth factors, evidenced by significantly increased expression of αSMA and myosin light chain kinase. Engineered media vessels composed of differentiated ASCs (ASC-SMCs) exhibited an elastic modulus (45.2 ± 18.9 kPa) between that of vessels of undifferentiated ASCs (71.8 ± 35.3 kPa) and control human aortic smooth muscle cells (HASMCs; 18.7 ± 5.49 kPa) (p<0.5). Tensile strength of vessels composed of ASCs (41.3 ± 15.7 kPa) and ASC-SMCs (37.3 ± 17.0 kPa) were higher compared to vessels of HASMCs (28.4 ± 11.2 kPa). ASC-based tissues exhibited a significant increase in collagen content and fiber maturity- both factors contribute to tissue strength and stability. Furthermore, vessels gained stability and a more-uniform single-tubular shape with longer-term 1-month culture. This work demonstrates efficacy of ASCs and PtFibs to create patient-specific vessels.
Topics: Humans; Tunica Media; Adventitia; Aorta; Collagen; Stem Cells
PubMed: 37738272
DOI: 10.1371/journal.pone.0291766 -
Polymers May 2024This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery...
This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery native vessels. Two segmented polyurethanes were synthesized using lysine (SPUUK) and ascorbic acid (SPUAA), and the resulting materials were used to create the intima and adventitia layers, respectively. In contrast, the media layer of the TVG was composed of a commercially available polyurethane, Pearlbond 703 EXP. For comparison purposes, single-layer vascular grafts (SVGs) from individual polyurethanes and a polyurethane blend (MVG) were made and tested similarly and evaluated according to the ISO 7198 standard. The TVG exhibited the highest circumferential tensile strength and longitudinal forces compared to single-layer vascular grafts of lower thicknesses made from the same polyurethanes. The TVG also showed higher suture and burst strength values than native vessels. The TVG withstood up to 2087 ± 139 mmHg and exhibited a compliance of 0.15 ± 0.1%/100 mmHg, while SPUUK SVGs showed a compliance of 5.21 ± 1.29%/100 mmHg, akin to coronary arteries but superior to the saphenous vein. An indirect cytocompatibility test using the MDA-MB-231 cell line showed 90 to 100% viability for all polyurethanes, surpassing the minimum 70% threshold needed for biomaterials deemed cytocompatibility. Despite the non-cytotoxic nature of the polyurethane extracts when grown directly on the surface, they displayed poor fibroblast adhesion, except for SPUUK. All vascular grafts showed hemolysis values under the permissible limit of 5% and longer coagulation times.
PubMed: 38794507
DOI: 10.3390/polym16101314 -
Journal of Veterinary Diagnostic... Jul 2024A 57-y-old male yellow-naped parrot () was presented because of lethargy, inappetence, and weight loss. Hematology and serum biochemistry were unremarkable, and imaging...
A 57-y-old male yellow-naped parrot () was presented because of lethargy, inappetence, and weight loss. Hematology and serum biochemistry were unremarkable, and imaging revealed a mass in the distal esophagus at the coelomic inlet. The luminal diameter of the esophagus was reduced in this area, and passage of ingesta was limited. Following gavage feeding, the patient died and was submitted for autopsy. At postmortem examination, the noted mass effect was a thickening of the distal esophagus with adherent, coalescing, soft, pale-tan plaques on the mucosal surface. Additional gross findings included pale-tan, opaque feed material oozing from the dorsum of the lungs and covering the cranial air sacs. Histology of the esophagus, esophageal-proventricular junction, and proximal proventriculus revealed an unencapsulated, infiltrative, transmural neoplasm that extended from the mucosal surface deep into the muscularis, almost to the adventitia. The neoplasm was composed of cuboidal cells arranged in islands and tubules, consistent with an adenocarcinoma, a rarely reported entity in the esophagus of psittacine birds and to our knowledge not reported previously at the esophageal-proventricular junction.
Topics: Animals; Male; Bird Diseases; Esophageal Neoplasms; Adenocarcinoma; Fatal Outcome; Proventriculus; Amazona; Parrots; Esophagus
PubMed: 38653775
DOI: 10.1177/10406387241247282