Smooth Muscle Layer Research Articles

Human acellular amniotic membrane/polycaprolactone vascular grafts prepared by electrospinning enable vascular remodeling in vivo

BackgroundVascular transplantation is an effective treatment for severe vascular lesions. The design of the bioactive and mechanical properties of small-caliber vascular grafts is critical for their application in tissue engineering. In this study, we sought to develope a small-caliber vascular graft by electrospinning a mixture of a human acellular amniotic membrane (HAAM) and polycaprolactone (PCL).ResultsMechanical tests showed that the vascular grafts were strong enough to endure stress from adjacent blood vessels and blood pressure. The biocompatibility of the HAAM/PCL vascular grafts was evaluated based on cell proliferation in vitro. The tubular formation test demonstrated that vascular grafts containing HAAM could improve human umbilical vein endothelial cell function, and in vivo implantation was performed by replacing the rat abdominal aorta. The HAAM/PCL vascular graft was found to promote attachment and endothelial cell retention. The regenerated smooth muscle layer was similar to native arteries' smooth muscle layer and the endothelium coverage was complete.ConclusionsThese results suggest that our constructs may be promising vascular graft candidates and can potentially be used to develop vascular grafts that can endothelialize rapidly in vivo.

Changes of the Urothelial Barrier System in the Cyclophosphamide-Induced Cystitis in Rats by Using a Newly Established "Inside-Out" Urinary Bladder Preparation.

The study was aimed to establish the "inside-out" preparation with the urothelium and investigate the changes in urothelial permeability of the cyclophosphamide (CYP)-induced cystitis model in rats. In female rats with or without CYP injection, the isolated whole bladder was utilized as an "inside-out" preparation with the urothelium, which was created by reversing the bladder from a top portion. The preparation was fixed in the organ bath, and instilled with a Krebs solution (0.5 mL) through the bladder neck. After it was kept under an isovolumetric condition, high K+ (KCl: 50 mM) or acetylcholine (ACh: 10 μM) was added into the organ bath. In the normal bladder, the intravesical pressure of the inside-out preparation with the urothelium did not change with the addition of KCl or ACh. Contrarily, in the CYP-injected bladder 24 or 48 h after injection of CYP, the intravesical pressure of the inside-out preparation increased with the addition of KCl or ACh. Histological examinations showed a denuded and/or cracked surface of the urothelial layer, and the intensity of uroplakin III staining of the urothelial layer decreased in the CYP-injected rats. The study demonstrated the bladder urothelium has robust barrier mechanisms for preventing the absorption of water (urine) under the normal condition. However, these barrier mechanisms were disrupted in the CYP-induced cystitis, suggesting that water and urine insults can be permeabilized into the urinary bladder, specifically to the smooth muscle layer.

Enhanced Purification of Uterine Smooth Muscle Cells from Adenomyosis Using a Novel Dual- Enzyme Digestion Method

Uterine adenomyosis causing attention to the abnormal smooth muscle layer has recently received increasing attention, which has created the need for a method that can efficiently collect high purity uterine smooth muscle cells (USMC) in a laboratory setting. In this study, we explored the composition ratios of the digestion solution to obtain the optimal digestion solution (DM4). Furthermore, we tested the superiority of the two methods of obtaining adenomyotic uterine smooth muscle by comparing DM4 with the conventional tissue adhesion method by growth rate, single-cell RNA sequencing, and purity of fluorescence identification. The results demonstrated that USMCs produced by the DM4 digestion method exhibited significantly higher rates of proliferation and were more effective in generating mature smooth muscle cells of high purity compared to those obtained using tissue adherence methods, which is more inclined to isolate the progenitor cell population. This study presents a reliable method for isolating USMCs and provides a solid foundation for future studies on the etiology and mechanism of adenomyosis.

Effect of Mepolizumab in airway’s remodelling in patients with late-onset severe asthma with an eosinophilic phenotype

BackgroundClinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling. ObjectiveWe thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care. MethodsMESILICO is a multicenter study involving 8 Pulmonology Departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy sub-study. The findings were related to clinical outcome. ResultsAfter 12 months, mepolizumab treatment was associated with significant improvements in lung function and ACT score, along with a significant decrease in severe exacerbation events (p<0.001). Thirty four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness and extent of epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). The extent of ASMLT reduction positively correlated with the submucosal eosinophil reduction (r= 0.599, p<0.001). ConclusionThis study identifies that 12 month of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, leads not only to clinical improvement but also reduces indices of airway tissue remodelling suggestive of a disease modifying effect.

Comparative microanatomy and histology of spinal and cerebral veins: Implications for dural arteriovenous fistula clinical presentations

Cranial dural arteriovenous fistulas (DAVFs) that display cortical venous drainage are at risk of hemorrhage, unlike spinal DAVFs, which seldom bleed. The underlying mechanism for this difference is poorly understood. We hypothesized that cerebral veins are more fragile than spinal veins due to differences in histologic compositions. Thus, spinal and cerebral veins from five formalin-fixed human cadavers were examined through macroscopic and histological analysis, using hematoxylin, eosin and safran (HES), and orcein stains to compare them. Twenty-four cerebral veins and thirteen spinal veins were analyzed. The mean diameter of the cerebral veins was 1.02 ± 0.59 mm, while that of spinal veins was 0.52 ± 0.26 mm (p = 0.003). The mean thickness of cerebral veins was similar to their spinal counterparts (0.09 ± 0.07 mm vs 0.06 ± 0.02 mm; p = 0.12). The mean diameter-to-thickness ratio was 13.76 ± 6.05 mm for cerebral veins and 10.06 ± 7.23 mm for spinal veins (p = 0.023). In most of the analyzed vessels, the venous wall was composed of endothelial cells resting on layers of smooth muscle, separated by elastica lamina. Cerebral and spinal veins exhibit distinct calibers while maintaining comparable wall thicknesses, resulting in a greater diameter-to-thickness ratio for cerebral veins compared to spinal veins. This difference may after their resistance to pressure. Furthermore, variations in the transparietal pressure gradient between cranial and spinal subarachnoid space, along with differences in arterial blood flow through the fistulous veins, might contribute to the observed differences in clinical presentation.

Heterozygous variants in the teashirt zinc finger homeobox 3 (TSHZ3) gene in human congenital anomalies of the kidney and urinary tract.

Around 180 genes have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in mice, and represent promising novel candidate genes for human CAKUT. In whole-exome sequencing data of two siblings with genetically unresolved multicystic dysplastic kidneys (MCDK), prioritizing variants in murine CAKUT-associated genes yielded a rare variant in the teashirt zinc finger homeobox 3 (TSHZ3) gene. Therefore, the role of TSHZ3 in human CAKUT was assessed. Twelve CAKUT patients from 9/301 (3%) families carried five different rare heterozygous TSHZ3 missense variants predicted to be deleterious. CAKUT patients with versus without TSHZ3 variants were more likely to present with hydronephrosis, hydroureter, ureteropelvic junction obstruction, MCDK, and with genital anomalies, developmental delay, overlapping with the previously described phenotypes in Tshz3-mutant mice and patients with heterozygous 19q12-q13.11 deletions encompassing the TSHZ3 locus. Comparable with Tshz3-mutant mice, the smooth muscle layer was disorganized in the renal pelvis and thinner in the proximal ureter of the nephrectomy specimen of a TSHZ3 variant carrier compared to controls. TSHZ3 was expressed in the human fetal kidney, and strongly at embryonic day 11.5-14.5 in mesenchymal compartments of the murine ureter, kidney, and bladder. TSHZ3 variants in a 5' region were more frequent in CAKUT patients than in gnomAD samples (p < 0.001). Mutant TSHZ3 harboring N-terminal variants showed significantly altered SOX9 and/or myocardin binding, possibly adversely affecting smooth muscle differentiation. Our results provide evidence that heterozygous TSHZ3 variants are associated with human CAKUT, particularly MCDK, hydronephrosis, and hydroureter, and, inconsistently, with specific extrarenal features, including genital anomalies.

Factors associated with uterine fibroids in women of reproductive age: A cross-sectional study

Background. Uterine fibroids is a benign monoclonal tumor originating from the smooth muscle layer of the uterus. Non-modifiable risk factors for the development of uterine fibroids, such as age, ethnicity, age at menarche, etc, have been studied quite extensively, while the role of many controllable factors remains debatable.The aim of the study. To identify the main modifiable factors associated with uterine fibroids in women of reproductive age living in the Baikal region, including certain ethnic groups.Materials and methods. We carried out a multicenter cross-sectional study in 2016–2019 in institutions of Irkutsk and Bokhan (Irkutsk region) and Ulan-Ude (Republic of Buryatia). The subjects of the study were women to have annual workplace medical examination. The study included 1,347 participants of reproductive age (34.33 ± 6.37 years) who met the inclusion criteria. Among all women included in the study, there were 867 (64.37 %) Caucasians, 361 (26.80 %) Asians, and 119 (8.83%) women of mixed (Caucasian-Asian), ethnicity. The research methods included a questionnaire, general clinical and gynecological examination, and pelvic ultrasound examination.Results. According to our study, the main non-modifiable factors associated with the presence of uterine fibroids were: Asian ethnicity; age at menarche 12–13 years; age of the study participant 40–44 years; menopausal symptoms; adenomyosis. The “controllable” factors included: city residency; body mass index over 40 kg/m2; history of abortions and miscarriages; metabolic syndrome; using combined oral contraceptives; lack of sexual activity; smoking; presence of anumber of occupational hazards.Conclusion. Our study identified the main controllable factors associated with the presence of uterine fibroids in a multiethnic population of women of reproductive age.

Ciliated foregut cysts involving the hepatopancreaticobiliary system: a clinicopathological evaluation with focus on atypical features

AimsForegut cystic malformations are rare developmental abnormalities, which may involve the hepatopancreaticobiliary tract (HPBT). These cysts are composed of inner ciliated epithelium; subepithelial connective tissue layer; smooth muscle layer; and...

Therapeutic diagnosis of atony of the detrusor muscle in a dog – case report

The urinary bladder is composed of layers of smooth muscle, known as the detrusor muscle. Urination occurs through the "detrusor reflex," which causes contraction of the bladder and relaxation of the urethra. Bethanechol, a parasympathomimetic drug, is indicated for dogs with hypocontractility or atonia of this muscle, aiding in bladder emptying. This report presents the case of a 9-year-old, 13.5 kg, spayed mixed-breed female dog, who experienced pollakiuria for three months. Initial supplementary exams revealed no significant alterations, except for a full and firm bladder upon palpation. Cystitis was identified, but the dog still could not urinate properly after the condition was resolved. Bethanechol was then administered as a diagnostic and therapeutic alternative, resulting in significant improvement. Thus, based on the response to the medication and the absence of other findings, it was concluded that the patient had detrusor muscle atonia. However, 23 days after the resolution of the condition, there was a worsening of clinical symptoms, necessitating more in-depth diagnostic evaluation to define the primary cause of the condition. Computed tomography helped exclude potential differential diagnoses related to spinal cord conditions. Nonetheless, more specific supplementary exams, such as magnetic resonance imaging and cerebrospinal fluid (CSF) analysis, would be necessary to reach a definitive diagnosis. This case highlights the importance of a comprehensive and continuous diagnostic approach for complex and recurrent urinary conditions in dogs.

Estrogen receptor alpha mediated repression of PRICKLE1 destabilizes REST and promotes uterine fibroid pathogenesis.

Uterine fibroids (leiomyomas), benign tumors of the myometrial smooth muscle layer, are present in over 75% of women, often causing severe pain, menorrhagia and reproductive dysfunction. The molecular pathogenesis of fibroids is poorly understood. We previously showed that the loss of REST (RE-1 Silencing Transcription factor), a tumor suppressor, in fibroids leads to activation of PI3K/AKT-mTOR pathway. We report here a critical link between estrogen receptor alpha (ERα) and the loss of REST, via PRICKLE1. PRICKLE1 expression is markedly lower in leiomyomas, and the suppression of PRICKLE1 significantly down regulates REST protein levels. Conversely, overexpression of PRICKLE1 resulted in the restoration of REST in cultured primary leiomyoma smooth muscle cells (LSMCs). Crucially, mice exposed neonatally to environmental estrogens, proven risk factors for fibroids, expressed lower levels of PRICKLE1 and REST in the myometrium. Using mice that lack either endogenous estrogen (Lhb -/- mice) or ERα (Esr1 -/- mice), we demonstrate that Prickle1 expression in the myometrium is suppressed by estrogen through ERα. Enhancer of zeste homolog 2 (EZH2) is known to participate in the repression of specific ERα target genes. Uterine leiomyomas express increased levels of EZH2 that inversely correlate with the expression of PRICKLE1. Using chromatin immunoprecipitation, we provide evidence for association of EZH2 with the PRICKLE1 promoter and for hypermethylation of H3K27 within the regulatory region of PRICKLE1 in leiomyomas. Additionally, siRNA mediated knockdown of EZH2 leads to restoration of PRICKLE1 in LSMCs. Collectively, our results identify a novel link between estrogen exposure and PRICKLE1/REST-regulated tumorigenic pathways in leiomyomas.

Seasonal Variation in TLR4 Expression in The Testis and Epididymis of Anatolian Ground Squirrels (Spermophilus xanthoprymnus): Insights from Non-Breeding Period of Pre-Hibernation and Hibernation

This study investigates the modulation of Toll-like receptor 4 (TLR4) expression within the testis and epididymis of Anatolian ground squirrels (Spermophilus xanthoprymnus) during the non-breeding period of pre-hibernation and hibernation. Immunohistochemical investigation showed that TLR4 was not detected in germ cells, Leydig cells, or Sertoli cells in the testicular tissue during the pre-hibernation period. Nevertheless, there was a presence of TLR4 in the vessels walls and certain interstitial cells within the intertubular regions. Epithelial cells in the caput, corpus, and cauda regions of the epididymis showed no TLR4 expression. However, it was observed in the vessel walls, smooth muscle layers, and some interstitial cells. TLR4 expression was seen in spermatogonia and primary spermatocytes during hibernation, with strong labeling observed in the vessel walls of the intertubular area. In contrast, TLR4 was detected in the epididymal epithelium, as well as in the smooth muscle layers and vessel walls throughout all segments. A notable upregulation in the expression of TLR4 in the testis was identified through quantitative image analysis during hibernation as compared to pre-hibernation. During pre-hibernation, the cauda segment of the epididymis exhibited the highest expression of TLR4, whereas during hibernation, the corpus segment demonstrated the highest expression. These findings suggest a dynamic modulation of TLR4 in response to hibernation, highlighting its potential role in reproductive function and immune adaptation.

Deep learning based uterine fibroid detection in ultrasound images

Uterine fibroids are common benign tumors originating from the uterus’s smooth muscle layer, often leading to symptoms such as pelvic pain, and reproductive issues. Early detection is crucial to prevent complications such as infertility or the need for invasive treatments like hysterectomy. One of the main challenges in diagnosing uterine fibroids is the lack of specific symptoms, which can mimic other gynecological conditions. This often leads to under-diagnosis or misdiagnosis, delaying appropriate management. In this research, an attention based fine-tuned EfficientNetB0 model is proposed for the classification of uterine fibroids from ultrasound images. Attention mechanisms, permit the model to focus on particular parts of an image and move forward the model’s execution by empowering it to specifically go to imperative highlights whereas overlooking irrelevant ones. The proposed approach has used a total of 1990 images divided into two classes: Non-uterine fibroid and uterine fibroid. The data augmentation methods have been connected to improve generalization and strength by exposing it to a wider range of varieties within the training data. The proposed model has obtained the value of accuracy as 0.99. Future research should focus on improving the accuracy and efficiency of diagnostic techniques, as well as evaluating their effectiveness in diverse populations with higher sensitivity and specificity for the detection of uterine fibroids, as well as biomarkers to aid in diagnosis.

MATERIAL PROPERTIES OF THE EMBRYONIC SMALL INTESTINE DURING BUCKLING MORPHOGENESIS.

During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops with wavelength and curvature that are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood.

Bi-layered Adipose Mesenchymal Cell Sheets Improve Bladder Compliance in Spinal Cord-Injured Rats.

To improve bladder compliance in patients with low-compliance bladders, augmentation cystoplasty with the intestinal tract is performed. However, the use of the intestinal tract often leads to serious surgical complications. Tissue engineering technologies have the potential to improve bladder compliance without using the intestinal tract. In this study, we fabricated bi-layered adipose-derived mesenchymal cell (AMC) sheets and then determined whether the bi-layered AMC sheets could improve bladder compliance in rats with spinal cord injury (SCI). The abdominal adipose tissues of green fluorescence protein (GFP)-transfected Sprague-Dawley (SD) rats were harvested, and the attached and proliferating cells on type I collagen were used as AMCs. The AMCs were then cultured on temperature-responsive culture dishes. After reaching over-confluence, the AMCs that maintained cell-cell contacts were detached from the dishes and applied to a gelatin hydrogel sheet. Then, another detached AMC monolayer was accumulated on the AMC monolayer-applied gelatin. Prior to 4 weeks of transplantation, the levels of T8-9 in the spinal cords of recipient SD rats were partially transected. After producing the bi-layered AMC sheets and the rats with SCI, the detrusor muscles of the anterior bladder walls of the rats with SCI were incised, and the bi-layered AMC sheet was patch-transplanted onto the exposed bladder epithelium (n = 8). As a control, the sham operation was performed (n = 7). Four weeks after the transplantation, bladder capacity and bladder compliance in AMC sheet-transplanted SCI rats were significantly higher than those in sham-operated control SCI rats. The smooth muscle layers in AMC sheet-transplanted bladders were significantly larger than those in control bladders. In addition, the collagen fibers in the AMC sheet-transplanted bladders were significantly smaller than those in the control bladders. Some GFP-positive transplanted AMCs differentiated into smooth muscle actin- or desmin-positive cells. Furthermore, GFP-positive cells secreted transforming growth factor-β1 or vascular endothelial growth factor. Therefore, this study showed that bi-layered AMC sheets could improve bladder compliance and bladder tissues in SCI rats.

Aquaporin 1 confers apoptosis resistance in pulmonary arterial smooth muscle cells from the SU5416 hypoxia rat model.

Pulmonary hypertension (PH) arises from increased pulmonary vascular resistance due to contraction and remodeling of the pulmonary arteries. The structural changes include thickening of the smooth muscle layer from increased proliferation and resistance to apoptosis. The mechanisms underlying apoptosis resistance in PH are not fully understood. In cancer cells, high expression of aquaporin 1 (AQP1), a water channel, is associated with apoptosis resistance. We showed AQP1 protein was expressed in pulmonary arterial smooth muscle cells (PASMCs) and upregulated in preclinical PH models. In this study, we used PASMCs isolated from control male rats and the SU5416 plus hypoxia (SuHx) model to test the role of AQP1 in modulating susceptibility to apoptosis. We found the elevated level of AQP1 in PASMCs from SuHx rats was necessary for resistance to apoptosis and that apoptosis resistance could be conferred by increasing AQP1 in control PASMCs. In exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, reducing the ratio of BAX to Bcl-2, consistent with apoptosis resistance. These results provide a mechanism by which AQP1 can regulate PASMC fate.

Management of supravalvular aortic stenosis with the Doty technique, in a South American pediatric center.

Supravalvular aortic stenosis (SVAS) is a congenital malformation associated with Williams-Beuren syndrome. It is characterized by severe stenosis of the sinotubular junction. The smooth muscle layer is thickened due to an alteration of the Elastin gene. The treatment is surgical and there are several techniques to relieve obstruction which range from the single-patch technique to the replacement of all three aortic sinuses with three patches. However, the optimal technique is still unclear. The objective of this article is to carry out a bibliographic review of surgical techniques for SVAS and the description of the application of the Doty technique for a 4-year-old infant at the Roberto Gilbert Elizalde Hospital.

Perivascular spaces around arteries exceed perivenous spaces in the mouse brain

The perivascular space (PVS) surrounds cerebral blood vessels and plays an important role in clearing waste products from the brain. Their anatomy and function have been described for arteries, but PVS around veins remain poorly characterized. Using in vivo 2-photon imaging in mice, we determined the size of the PVS around arteries and veins, and their connection with the subarachnoid space. After infusion of 70 kD FITC-dextran into the cerebrospinal fluid via the cisterna magna, labeled PVS were evident around arteries, but veins showed less frequent labeling of the PVS. The size of the PVS correlated with blood vessel size for both pial arteries and veins, but not for penetrating vessels. The PVS around pial arteries and veins was separated from the subarachnoid space by a thin meningeal layer, which did not form a barrier for the tracer. In vivo, FITC-dextran signal was observed adjacent to the vessel wall, but minimally within the wall itself. Post-mortem, there was a significant shift in the tracer's location within the arterial wall, extending into the smooth muscle layer. Taken together, these findings suggest that the PVS around veins has a limited role in the exchange of solutes between CSF and brain parenchyma.

Systematic histology and evidence for the male reproductive activity of Amphibalanus amphitrite (Darwin, 1854)

AbstractThe striped acorn barnacle, Amphibalanus amphitrite, a taxon of Balanidae, is commonly found along Thailand's coastline. In this study, we used histological methods to describe the microscopic anatomy of A. amphitrite. All samples (n = 30) were obtained from the seagrass beds of Libong Island, Thailand, in the Andaman Sea. Histological observation of various longitudinal sections from specimens of A. amphitrite provides clear insights into the organization of organ systems in the species. The digestive tract was observed to be mainly divided into four subregions, including the cuticle‐lined mouth and esophagus, which is characterized by a high columnar epithelium, the stomach, and the intestine. The accessory organ, including the digestive gland, exhibited lobulated structures and was covered with low columnar epithelial cells on a thin layer of smooth muscle. Furthermore, we examined the reproductive system, including both the ovary and testes, as well as the process of gametogenesis. Testicular development was predominantly observed during active breeding seasons throughout the observation.

Collagen 17A1 in the Urothelium Regulates Epithelial Cell Integrity and Local Immunologic Responses in Obstructive Uropathy

Collagen 17A1 (COL17A1), an epidermal hemidesmosome component, is ectopically induced in the urothelium of mouse and human renal pelvis (RP) in parallel with urinary tract-associated lymphoid structure development. Here, COL17A1 was induced in obstructive uropathy-prone ureter of humans and cats. To ascertain its function, murine urinary organs with unilateral ureteral obstruction (UUO) were analyzed during 1 week after surgery. One day after UUO, COL17A1 expression increased in urothelial cells of RP and ureter, and was positively correlated with renal tubulointerstitial lesions. A portion of RP where the smooth muscle layer from the ureter was interrupted was sensitive to urothelium deciduation and COL17A1 induction, showing urine leaked from the RP lumen into the parenchyma. After urine stimulation, cultured immune cells expressed Cxcl2, also up-regulated in CD11b+ cells following COL17A1 stimulation. One day after UUO, CXCL2+ CD11b+ cells infiltrated the urothelium-disrupted area. However, these numbers were significantly lower in Col17a1-deficient mice. COL17A1+ urothelial cells partially co-expressed cytokeratin-14, a progenitor cell marker for urothelium, whereas Col17a1-deficient mice had lower numbers of cytokeratin-14+ cells. Gene Ontology analysis revealed that expression of epithelial- and immune-associated genes was up-regulated and down-regulated, respectively, in the ureter of Col17a1-deficient mice 4 days after UUO. Thus, COL17A1 maintains urothelium integrity by regulating urothelial cell adhesion, proliferation, and differentiation, and activates local immune responses during obstructive uropathy in mammals.

Harnessing the potential of monocytes/macrophages to regenerate tissue-engineered vascular grafts.

Cell-free tissue-engineered vascular grafts provide a promising alternative to treat cardiovascular disease, but timely endothelialization is essential for ensuring patency and proper functioning post-implantation. Recent studies from our lab showed that blood cells like monocytes (MCs) and macrophages (Mϕ) may contribute directly to cellularization and regeneration of bioengineered arteries in small and large animal models. While MCs and Mϕ are leucocytes that are part of the innate immune response, they share common developmental origins with endothelial cells (ECs) and are known to play crucial roles during vessel formation (angiogenesis) and vessel repair after inflammation/injury. They are highly plastic cells that polarize into pro-inflammatory and anti-inflammatory phenotypes upon exposure to cytokines and differentiate into other cell types, including EC-like cells, in the presence of appropriate chemical and mechanical stimuli. This review focuses on the developmental origins of MCs and ECs; the role of MCs and Mϕ in vessel repair/regeneration during inflammation/injury; and the role of chemical signalling and mechanical forces in Mϕ inflammation that mediates vascular graft regeneration. We postulate that comprehensive understanding of these mechanisms will better inform the development of strategies to coax MCs/Mϕ into endothelializing the lumen and regenerate the smooth muscle layers of cell-free bioengineered arteries and veins that are designed to treat cardiovascular diseases and perhaps the native vasculature as well.