Background: The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery.
Results: We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics.
The mechanistic underpinnings of breast cancer recurrence following periods of dormancy are largely undetermined. A new study in PLOS Biology reveals that docetaxel-induced injury of tumour stromal cells stimulates the release of cytokines that support dormancy escape of breast cancer cells.
View Article and Find Full Text PDFWnt and Hh are known signalling pathways involved in neural differentiation and recent work has shown the cell cycle regulator, Never in Mitosis Kinase 2 (Nek2) is able to regulate both pathways. Despite its known function in pathway regulation, few studies have explored Nek2 within embryonic development. The P19 embryonal carcinoma cell model was used to investigate Nek2 and neural differentiation through CRISPR knockout and overexpression studies.
View Article and Find Full Text PDFThe secretome of mesenchymal stromal cells (MSCs) is enriched for biotherapeutic effectors contained within and independent of extracellular vesicles (EVs) that may support tissue regeneration as an injectable agent. We have demonstrated that the intrapancreatic injection of concentrated conditioned media (CM) produced by bone marrow MSC supports islet regeneration and restored glycemic control in hyperglycemic mice, ultimately providing a platform to elucidate components of the MSC secretome. Herein, we extend these findings using human pancreas-derived MSC (Panc-MSC) as "biofactories" to enrich for tissue regenerative stimuli housed within distinct compartments of the secretome.
View Article and Find Full Text PDFFluorescent-activated cell sorting (FACS) remains a powerful tool to enrich blood-derived progenitor cells for the establishment of highly proliferative endothelial colony-forming cells (ECFC). Further investigation remains necessary to determine whether the retention of progenitor cell phenotypes after expansion can identify ECFC with enhanced proangiogenic and regenerative functions. This study employed FACS purification to segregate umbilical cord blood-derived ECFC using conserved provascular progenitor cell markers CD34 or aldehyde dehydrogenase (ALDH) activity.
View Article and Find Full Text PDFMultipotent/mesenchymal stromal cells (MSCs) exist within a variety of postnatal tissues; however, global proteomic analyses comparing tissue-specific MSC are limited. Using human bone marrow (BM)-derived MSCs as a gold standard, we used label-free mass spectrometry and functional assays to characterize the proteome, secretome, and corresponding function of human pancreas-derived MSCs (Panc-MSCs) with a classical phenotype (CD90+/CD73+/CD105+/CD45-/CD31-). Both MSC subtypes expressed mesenchymal markers vimentin, α-SMA, and STRO-1; however, expression of nestin was increased in Panc-MSCs.
View Article and Find Full Text PDFRecently in Nature, Wimmer et al. (2019) reported on the development of a human organoid model of vascular development recapitulating vascular pathology during type 2 diabetes. Integration of these organoids into the vasculature of immunodeficient mice may provide cardiometabolic researchers with a "personalized" platform for novel therapeutic discovery.
View Article and Find Full Text PDFBackground: Platelet microparticles (PMPs) and their abundance in the blood are a prognostic biomarker in thrombotic disorders and cancer. Nanoscale flow cytometry (nFC) is ideal for high-throughput analysis of PMPs but these clinical assays have not been developed previously.
Objective: This article demonstrates that nFC is a suitable technology to enumerate PMPs present in plasma samples in a clinical setting.
Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, , an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis.
View Article and Find Full Text PDFIslet regeneration is stimulated after transplantation of human umbilical cord blood (UCB) hematopoietic progenitor cells with high aldehyde dehydrogenase (ALDH)-activity into NOD/SCID mice with streptozotocin (STZ)-induced β cell ablation. ALDH progenitor cells represent a rare subset within UCB that will require expansion without the loss of islet regenerative functions for use in cell therapies. ALDH cells efficiently expand (>70-fold) under serum-free conditions; however, high ALDH-activity is rapidly diminished during culture coinciding with emergence of a committed megakaryocyte phenotype CD41+/CD42+/CD38+.
View Article and Find Full Text PDFBlood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDH ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.
View Article and Find Full Text PDFA promising strategy for treating peripheral ischemia involves the delivery of stem cells to promote angiogenesis through paracrine signaling. Treatment success depends on cell localization, retention, and survival within the mechanically dynamic intramuscular (IM) environment. Herein we describe an injectable, in situ-gelling hydrogel for the IM delivery of adipose-derived stem/stromal cells (ASCs), specifically designed to withstand the dynamic loading conditions of the lower limb and facilitate cytokine release from encapsulated cells.
View Article and Find Full Text PDFUncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDH cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (<0.5%) of these cells.
View Article and Find Full Text PDFDuring culture expansion, multipotent mesenchymal stromal cells (MSCs) differentially express aldehyde dehydrogenase (ALDH), an intracellular detoxification enzyme that protects long-lived cells against oxidative stress. Thus, MSC selection based on ALDH-activity may be used to reduce heterogeneity and distinguish MSC subsets with improved regenerative potency. After expansion of human bone marrow-derived MSCs, cell progeny was purified based on low versus high ALDH-activity (ALDH ) by fluorescence-activated cell sorting, and each subset was compared for multipotent stromal and provascular regenerative functions.
View Article and Find Full Text PDFHuman umbilical cord blood (UCB) hematopoietic progenitor cells (HPC) purified for high aldehyde dehydrogenase activity (ALDH(hi) ) stimulate islet regeneration after transplantation into mice with streptozotocin-induced β cell deletion. However, ALDH(hi) cells represent a rare progenitor subset and widespread use of UCB ALDH(hi) cells to stimulate islet regeneration will require progenitor cell expansion without loss of islet regenerative functions. Here we demonstrate that prospectively purified UCB ALDH(hi) cells expand efficiently under serum-free, xeno-free conditions with minimal growth factor supplementation.
View Article and Find Full Text PDFClin Med Insights Blood Disord
December 2014
We report a rare case of anemia and thrombocytopenia as a result of uterine fibroid and adenomyosis, complicated by immune thrombocytopenic purpura (ITP). Symptoms were presented as menorrhagia and metrorrhagia in a 34-year-old African American woman, who was later treated with blood and platelet transfusion and iron therapy with steroids. Uterine fibroids are commonly found to cause hematologic disturbances such as anemia and reactive thrombocytosis and, less commonly, thrombocytopenia.
View Article and Find Full Text PDF