Growth Of Stem Cells Research Articles

Periostin/Bone Morphogenetic Protein 1 axis axis regulates proliferation and osteogenic differentiation of sutured mesenchymal stem cells and affects coronal suture closure in the TWIST1+/− mouse model of craniosynostosis

Background and objectiveThe pathogenesis of coronal suture craniosynostosis is often attributed to the dysregulated cellular dynamics, particularly the excessive proliferation and abnormal osteogenic differentiation of suture cells. Despite its clinical significance, the molecular mechanims of this condition remain inadequately understood. This study is dedicated to exploring the influence of the Periostin/Bone Morphogenetic Protein 1 (BMP1) axis on the growth and osteogenic maturation of Suture Mesenchymal Stem Cells (SMSCs), which are pivotal in suture homeostasis. MethodsNeonatal TWIST Basic Helix-Loop-Helix Transcription Factor 1 heterozygous (TWIST1+/−) mice, aged one day, were subjected to adenoviral vector-mediated Periostin upregulation. To modulate Periostin/BMP1 levels in SMSCs, we employed siRNA and pcDNA 3.1 vectors. Histological and molecular characterizations, including hematoxylin and eosin staining, Western blot, and immunohistochemistry were employed to study suture closure phenotypes and protein expression patterns. Cellular assays, encompassing colony formation, 5-ethynyl-2'deoxyuridine, and wound healing tests were conducted to analyze SMSC proliferation and migration. Osteogenic differentiation was quantified using Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) staining, while protein markers of proliferation and differentiation were evaluated by Western blotting. The direct interaction between Periostin and BMP1 was validated through co-immunoprecipitation assays.ResultsIn the TWIST1+/− model, an upregulation of Periostin coupled with a downregulation of BMP1 was observed. Augmenting Periostin expression mitigated craniosynostosis. In vitro, overexpression of Periostin or BMP1 knockdown suppressed SMSC proliferation, migration, and osteogenic differentiation. Periostin knockdown manifested an inverse biological impact. Notably, the suppressive influence of Periostin overexpression on SMSCs was effectively counteracted by upregulating BMP1. There was a direct interaction between Periostin and BMP1.ConclusionThese findings underscore the significance of the Periostin/BMP1 axis in regulating craniosynostosis and SMSC functions, providing new insights into the molecular mechanisms of craniosynostosis and potential targets for therapeutic intervention.

3D Stem Cell Spheroids with 2D Hetero-Nanostructures for In Vivo Osteogenic and Immunologic Modulated Bone Repair.

3D stem cell spheroids have immense potential for various tissue engineering applications. However, current spheroid fabrication techniques encounter cell viability issues due to limited oxygen access for cells trapped within the core, as well as nonspecific differentiation issues due to the complicated environment following transplantation. In this study, functional 3D spheroids are developed using mesenchymal stem cells with 2D hetero-nanostructures (HNSs) composed of single-stranded DNA (ssDNA) binding carbon nanotubes (sdCNTs) and gelatin-bind black phosphorus nanosheets (gBPNSs). An osteogenic molecule, dexamethasone (DEX), is further loaded to fabricate an sdCNTgBP-DEX HNS. This approach aims to establish a multifunctional cell-inductive 3D spheroid with improved oxygen transportation through hollow nanotubes, stimulated stem cell growth by phosphate ions supplied from BP oxidation, in situ immunoregulation, and osteogenesis induction by DEX molecules after implantation. Initial transplantation of the 3D spheroids in rat calvarial bone defect shows in vivo macrophage shifts to an M2 phenotype, leading to a pro-healing microenvironment for regeneration. Prolonged implantation demonstrates outstanding in vivo neovascularization, osteointegration, and new bone regeneration. Therefore, these engineered 3D spheroids hold great promise for bone repair as they allow for stem cell delivery and provide immunoregulative and osteogenic signals within an all-in-one construct.

Scutellarin, a flavonoid compound from Scutellaria barbata, suppresses growth of breast cancer stem cells in vitro and in tumor-bearing mice

BackgroundScutellaria barbata D. Don (SB), commonly known as Ban Zhi Lian and firstly documented by Shigong Chen, is a dried whole plant that has been studied for its therapeutic effects on breast cancer, colon cancer, and prostate cancer. Among its various compounds, scutellarin (SCU) has been demonstrated with anti-tumor effects. PurposeThis study aimed to evaluate the effects of SB water extract (SBW) and scutellarin on breast cancer stem cells (BCSCs), and to investigate their potential therapeutic effects on breast tumors in mice. MethodsBCSCs were enriched from human breast cancer cells (MDA-MB-231 and MDA-MB-361) and their characteristics were analyzed. The effects of varying concentrations of SBW and scutellarin on cell viability, proliferation, self-renewal, and migration abilities were studied, along with the underlying mechanisms. The in vivo anti-tumor effects of scutellarin were further evaluated in SCID/NOD mice. Firstly, mice were inoculated with naïve BCSCs and subjected to treatment with scutellarin or vehicle. Secondly, BCSCs were pre-treated with scutellarin or vehicle prior to inoculation into mice. ResultsThe derived BCSCs expressed CD44, CD133 and ALDH1, but not CD24, indicating that BCSCs have been successfully induced from both MDA-MB-231 and MDA-MB-361 cells. Both SBW and scutellarin reduced the viability, proliferation, sphere and colony formation, and migration of BCSCs. In mice with tumors derived from naïve BCSCs, scutellarin significantly reduced tumor growth, expression of proliferative (Ki67) and stem cell markers (CD44), and lung metastasis. In addition, pre-treatment with scutellarin also slowed tumor growth. Western blot results suggested the involvement of Wnt/β-catenin, NF-κB, and PTEN/Akt/mTOR signaling pathways underlying the inhibitory effects of scutellarin. ConclusionOur study demonstrated for the first time that both SB water extract and scutellarin could reduce the proliferation and migration of BCSCs in vitro. Scutellarin was shown to possess novel inhibitory activities in BCSCs progression. These findings suggest that Scutellaria barbata water extract, in particular, scutellarin, may have potential to be further developed as an adjuvant therapy for reducing breast cancer recurrence.

R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient

Establishment of the left-right (LR, sinistral, dextral) body axis in many vertebrate embryos relies on cilia-driven leftward fluid flow within an LR organizer (LRO). A cardinal question is how leftward flow triggers symmetry breakage. The chemosensation model posits that ciliary flow enriches a signaling molecule on the left side of the LRO that promotes sinistral cell fate. However, the nature of this sinistralizing signal has remained elusive. In the Xenopus LRO, we identified the stem cell growth factor R-Spondin 2 (Rspo2) as a symmetrically expressed, sinistralizing signal. As predicted for a flow-mediated signal, Rspo2 operates downstream of leftward flow but upstream of the asymmetrically expressed gene dand5. Unexpectedly, in LR patterning, Rspo2 acts as an FGF receptor antagonist: Rspo2 via its TSP1 domain binds Fgfr4 and promotes its membrane clearance by Znrf3-mediated endocytosis. Concordantly, we find that at flow-stage, FGF signaling is dextralizing and forms a gradient across the LRO, high on the dextral- and low on the sinistral side. Rspo2 gain- and loss-of function equalize this FGF signaling gradient and sinistralize and dextralize development, respectively. We propose that leftward flow of Rspo2 produces an FGF signaling gradient that governs LR-symmetry breakage.

TERT mediates the U-shape of glucocorticoids effects in modulation of hippocampal neural stem cells and associated brain function.

Glucocorticoids (GCs) are steroidal hormones produced by the adrenal cortex. A physiological-level GCs have a crucial function in maintaining many cognitive processes, like cognition, memory, and mood, however, both insufficient and excessive GCs impair these functions. Although this phenomenon could be explained by the U-shape of GC effects, the underlying mechanisms are still not clear. Therefore, understanding the underlying mechanisms of GCs may provide insight into the treatments for cognitive and mood-related disorders. Consecutive administration of corticosterone (CORT, 10 mg/kg, i.g.) proceeded for 28 days to mimic excessive GCs condition. Adrenalectomy (ADX) surgery was performed to ablate endogenous GCs in mice. Microinjection of 1 μL of Ad-mTERT-GFP virus into mouse hippocampus dentate gyrus (DG) and behavioral alterations in mice were observed 4 weeks later. Different concentrations of GCs were shown to affect the cell growth and development of neural stem cells (NSCs) in a U-shaped manner. The physiological level of GCs (0.01 μM) promoted NSC proliferation invitro, while the stress level of GCs (10 μM) inhibited it. The glucocorticoid synthesis blocker metyrapone (100 mg/kg, i.p.) and ADX surgery both decreased the quantity and morphological development of doublecortin (DCX)-positive immature cells in the DG. The physiological level of GCs activated mineralocorticoid receptor and then promoted the production of telomerase reverse transcriptase (TERT); in contrast, the stress level of GCs activated glucocorticoid receptor and then reduced the expression of TERT. Overexpression of TERT by AD-mTERT-GFP reversed both chronic stresses- and ADX-induced deficiency of TERT and the proliferation and development of NSCs, chronic stresses-associated depressive symptoms, and ADX-associated learning and memory impairment. The bidirectional regulation of TERT by different GCs concentrations is a key mechanism mediating the U-shape of GC effects in modulation of hippocampal NSCs and associated brain function. Replenishment of TERT could be a common treatment strategy for GC dysfunction-associated diseases.

The effect of nano-natural biomaterial on stimulation of RADMSCs toward osteogenesis: an in vitro study

In recent years, natural biomaterials have been the focal point of most biomedical investigations. To prepare the Ostrich Eggshell/Hydroxyapatite (OE/HA) powder scaffolds, OE powder was immersed in 1% Triton X-100 for 24 h and then autoclaved twice. Medical grade HA was combined with pulverized OE at different ratios to yield three different OE/HA powder scaffolds. The resultant scaffolds underwent characterization experiments using different techniques, including FTIR, XRD, radiography, and SEM analyses. Rabbit adipose-derived mesenchymal stem cells (RADMSCs) were isolated from adipose tissues and characterized by flow cytometry. A direct contact test was performed for the cytotoxicity test using L929 cells. Cell adhesion was validated using SEM imaging, viability was assessed using DAPI and Annexin V/PI staining, and osteogenic differentiation was investigated using the ALP assay. The cytotoxicity assay using L929 cells verified that the OE/HA powder scaffold is safe and further functional experiments could be carried out. Behavioral assays, radiography, surface markers, surface topography analyses, and viability tests yielded promising results confirming cellular acceptance of the scaffold. In the present study, we provided evidence that the prepared OE/HA scaffold is not only cytocompatible but also can enhance mesenchymal stem cell adhesion, growth, and osteogenic differentiation in vitro.

The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study.

Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism. Inflammatory cytokines in 30,155 individuals of European ancestry with hypothyroidism and in a GWAS summary containing 8,293 healthy participants were included in the study for bidirectional two-sample MR analysis. We utilized inverse variance weighting (IVW), weighted median (WM), and Mendelian randomization-Egger (MR-Egger) methods. Multiple sensitivity analyses, including MR-Egger intercept test, leave-one-out analysis, funnel plot, scatterplot, and MR-PRESSO, were applied to evaluate assumptions. We found evidence of a causal effect of IL-7 and macrophage inflammatory protein-1β (MIP-1β) on the risk of hypothyroidism, and a causal effect of hypothyroidism on several cytokines, including granulocyte colony-stimulating factor (G-CSF), IL-13, IL-16, IL-2rα, IL-6, IL-7, IL-9, interferon-γ-inducible protein 10 (IP10), monokine induced by interferon (IFN)-γ (MIG), macrophage inflammatory protein-1β (MIP-1β), stem cell growth factors-β (SCGF-β), stromal cell derived factor-1α (SDF-1α), and tumor necrosis factor-α (TNF-α). Our study suggests that IL-7 and MIP-1β may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications. However, further experimental studies are needed to validate the causal relationships and the potential of these cytokines as drug targets.

Microporous Fluorescent Poly(D,L-lactide) Acid-Carbon Nanodot Scaffolds for Bone Tissue Engineering Applications.

In this study, we introduce novel microporous poly(D,L-lactide) acid-carbon nanodot (PLA-CD) nanocomposite scaffolds tailored for potential applications in image-guided bone regeneration. Our primary objective was to investigate concentration-dependent structural variations and their relevance to cell growth, crucial aspects in bone regeneration. The methods employed included comprehensive characterization techniques such as DSC/TGA, FTIR, rheological, and degradation assessments, providing insights into the scaffolds' thermoplastic behavior, microstructure, and stability over time. Notably, the PLA-CD scaffolds exhibited distinct self-fluorescence, which persisted after 21 days of incubation, allowing detailed visualization in various multicolor modalities. Biocompatibility assessments were conducted by analyzing human adipose-derived stem cell (hADSC) growth on PLA-CD scaffolds, with results substantiated through cell viability and morphological analyses. hADSCs reached a cell viability of 125% and penetrated throughout the scaffold after 21 days of incubation. These findings underscore the scaffolds' potential in bone regeneration and fluorescence imaging. The multifunctional nature of the PLA-CD nanocomposite, integrating diagnostic capabilities with tunable properties, positions it as a promising candidate for advancing bone tissue engineering. Our study not only highlights key aspects of the investigation but also underscores the scaffolds' specific application in bone regeneration, providing a foundation for further research and optimization in this critical biomedical field.

Simvastatin Induces Apoptosis but Attenuates Migration in SCAPs

Simvastatin has emerged as having a promising role in controlling stem cell behaviours. This study aimed to evaluate the effects of simvastatin on the viability, growth, and migration of stem cells isolated from apical papillae (SCAPs) in vitro. SCAPs were isolated and characterised. The viability and proliferation were assessed using live/dead and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, respectively. Cell migration was evaluated using scratch assays. Cell cycle progression and apoptosis were examined using flow cytometry analysis. Simvastatin at a concentration of 100 to 1000 nM did not exhibit cytotoxicity. Simvastatin reduced cell numbers at days 3 and 7. In addition, simvastatin markedly decreased colony formation in both colony number and cell density in a dose-dependent manner. An increase in apoptosis was observed at day 7. There was statistically significant increased in sub G0 population. An in vitro cell migration was attenuated in a dose-dependent manner. Simvastatin affects SCAPs' viability, proliferation, and cell migration. The reduction of cell viability at day 7 could be due to apoptotic induction.

Role of miRNA in Cardiovascular Diseases in Children-Systematic Review.

The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.

Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease.

Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2-sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome-wide association study of 8293 European participants. Summary-level data on CAD were derived from a large genome-wide association study (71 602 cases and 260 875 controls). We used the inverse-variance-weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR-Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni-adjusted level of significance (P<1.79×10-3). The odds ratio was 1.20 (95% CI, 1.08-1.33; P=6.83×10-4) per 1-SD increase in macrophage migration inhibitory factor. Colocalization analyses supported our MR findings. Additionally, we found suggestive evidence between the genetic effects of stem cell growth factor-β and the risk of CAD (odds ratio, 0.95 [95% CI, 0.91-0.98]; P=0.007). Our findings suggested a risk-increasing effect of macrophage migration inhibitory factor level on the development of CAD. The roles of these inflammatory factors for CAD warrant further investigation.

Stem Cell Growth Factor-β as a Predictive Biomarker of Response to Chemotherapy and Prognosis in Patients with Advanced-Stage Hepatocellular Carcinoma: A Retrospective Study.

In this retrospective study, we investigated the potential application of serum stem cell growth factor beta (SCGF-β) as a biomarker for predicting the therapeutic response and prognosis in patients with hepatocellular carcinoma (HCC) undergoing atezolizumab and bevacizumab (Atz/Bev) combination therapy. Pre- and post-treatment serum SCGF-β levels were measured and analyzed in relation to treatment outcomes and overall survival (OS). Pretreatment SCGF-β levels were associated with treatment response. Patients with SCGF-β levels exceeding the 163,295 pg/mL cutoff experienced significantly reduced OS, with a median OS of 12.03 months, compared to 28.87 months in those with SCGF-β levels at or below this threshold. These findings suggest that SCGF-β can serve as a predictive marker for clinical outcomes in HCC treatment, highlighting the need for prospective studies to further validate these results and clarify the mechanisms underlying SCGF-β-related therapeutic resistance.

Preparation of gallic acid-containing PCL/gelatine scaffolds as an efficient drug delivery system for growth and proliferation of human stem cells

Preparation of gallic acid-containing PCL/gelatine scaffolds as an efficient drug delivery system for growth and proliferation of human stem cells

Effects of Oral Cavity Stem Cell Sources and Serum-Free Cell Culture on Hydrogel Encapsulation of Mesenchymal Stem Cells for Bone Regeneration: An In Vitro Investigation.

To develop a stem cell delivery model and improve the safety of stem cell transplantation for bone regeneration, this study aimed to determine the effects of stem cell sources, serum-free cell culture, and hydrogel cell encapsulation on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs) from the oral cavity. The study groups were categorized according to stem cell sources into buccal fat pad adipose (hBFP-ADSCs) (Groups 1, 4, and 7), periodontal ligament (hPDLSCs) (Groups 2, 5, and 8), and dental pulp-derived stem cells (hDPSCs) (Groups 3, 6, and 9). MSCs from each source were isolated and expanded in three types of sera: fetal bovine serum (FBS) (Groups 1-3), human serum (HS) (Groups 4-6), and synthetic serum (SS) (StemPro™ MSC SFM) (Groups 7-9) for monolayer (m) and hydrogel cell encapsulation cultures (e). Following this, the morphology, expression of MSC cell surface antigens, growth, and osteogenic differentiation potential of the MSCs, and the expression of adhesion molecules were analyzed and compared. SS decreased variations in the morphology and expression levels of cell surface antigens of MSCs from three cell sources (Groups 7m-9m). The levels of osteoblastic differentiation of the hPDLSCs and hBFP-ADSCs were increased in SS (Groups 8m and 7m) and the cell encapsulation model (Groups 1e, 4e, 7e-9e), but the promoting effects of SS were decreased in a cell encapsulation model (Groups 7e-9e). The expression levels of the alpha v beta 3 (ITG-αVβ3) and beta 1 (ITG-β1) integrins in the encapsulated cells in FBS (Group 1e) were higher than those in the SS (Group 7e). Human PDLSCs and BFP-ADSCs were the optimum stem cell source for stem cell encapsulation by using nanohydroxyapatite-calcium carbonate microcapsule-chitosan/collagen hydrogel in serum-free conditions.

Paneth-like cells produced from OLFM4+ stem cells support OLFM4+ stem cell growth in advanced colorectal cancer

Tumor tissues consist of heterogeneous cells that originate from stem cells; however, their cell fate determination program remains incompletely understood. Using patient-derived organoids established from patients with advanced colorectal cancer (CRC), we evaluated the potential of olfactomedin 4 (OLFM4)+ stem cells to produce a bifurcated lineage of progenies with absorptive and secretory properties. In the early phases of organoid reconstruction, OLFM4+ cells preferentially gave rise to secretory cells. Additionally, we found that Paneth-like cells, which do not exist in the normal colon, were induced in response to Notch signaling inhibition. Video recordings of single OLFM4+ cells revealed that organoids containing Paneth-like cells were effectively propagated and that their selective ablation led to organoid collapse. In tumor tissues, Paneth-like cells were identified only in the region where tumor cells lost cell adhesion. These findings indicate that Paneth-like cells are directly produced by OLFM4+ stem cells and that their interaction contributes to tumor formation by providing niche factors. This study reveals the importance of the cell fate specification program for building a complete tumor cellular ecosystem, which might be targeted with novel therapeutics.

Cytocompatible and osteoconductive silicon oxycarbide glass scaffolds 3D printed by DLP: a potential material for bone tissue regeneration.

Bone lesions affect individuals of different age groups, compromising their daily activities and potentially leading to prolonged morbidity. Over the years, new compositions and manufacturing technologies were developed to offer customized solutions to replace injured tissue and stimulate tissue regeneration. This work used digital light processing (DPL) technology for three-dimensional (3D) printing of porous structures using pre-ceramic polymer, followed by pyrolysis to obtain SiOC vitreous scaffolds. The SiOC scaffolds produced had an amorphous structure (compatible with glass) with an average porosity of 72.69% ± 0.99, an average hardness of 935.1 ± 71.0HV, and an average maximum flexural stress of 7.8 ± 1.0MPa, similar to cancellous bone tissue. The scaffolds were not cytotoxic and allowed adult stem cell adhesion, growth, and expansion. After treatment with osteoinductive medium, adult stem cells in the SiOC scaffolds differentiated to osteoblasts, assuming a tissue-like structure, with organization in multiple layers and production of a dense fibrous matrix rich in hydroxyapatite. The in vitro analyses supported the hypothesis that the SiOC scaffolds produced in this work were suitable for use as a bone substitute for treating critically sized lesions, with the potential to stimulate the gradual process of regeneration of the native tissue. The data obtained stimulate the continuity of studies with the SiOC scaffolds developed in this work, paving the way for evaluating safety and biological activity in vivo.

M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury

Electroconductive hydrogels offer a promising avenue for enhancing the repair efficacy of spinal cord injuries (SCI) by restoring disrupted electrical signals along the spinal cord’s conduction pathway. Nonetheless, the application of hydrogels composed of diverse electroconductive materials has demonstrated limited capacity to mitigate the post-SCI inflammatory response. Recent research has indicated that the transplantation of M2 microglia effectively fosters SCI recovery by attenuating the excessive inflammatory response. Exosomes (Exos), small vesicles discharged by cells carrying similar biological functions to their originating cells, present a compelling alternative to cellular transplantation. This investigation endeavors to exploit M2 microglia-derived exosomes (M2-Exos) successfully isolated and reversibly bonded to electroconductive hydrogels through hydrogen bonding for synergistic promotion of SCI repair to synergistically enhance SCI repair. In vitro experiments substantiated the significant capacity of M2-Exos-laden electroconductive hydrogels to stimulate the growth of neural stem cells and axons in the dorsal root ganglion and modulate microglial M2 polarization. Furthermore, M2-Exos demonstrated a remarkable ability to mitigate the initial inflammatory reaction within the injury site. When combined with the electroconductive hydrogel, M2-Exos worked synergistically to expedite neuronal and axonal regeneration, substantially enhancing the functional recovery of rats afflicted with SCI. These findings underscore the potential of M2-Exos as a valuable reparative factor, amplifying the efficacy of electroconductive hydrogels in their capacity to foster SCI rehabilitation.

Lymphatic endothelial-like cells promote glioblastoma stem cell growth through cytokine-driven cholesterol metabolism.

Glioblastoma is the most lethal primary brain tumor with glioblastoma stem cells (GSCs) atop a cellular hierarchy. GSCs often reside in a perivascular niche, where they receive maintenance cues from endothelial cells, but the role of heterogeneous endothelial cell populations remains unresolved. Here, we show that lymphatic endothelial-like cells (LECs), while previously unrecognized in brain parenchyma, are present in glioblastomas and promote growth of CCR7-positive GSCs through CCL21 secretion. Disruption of CCL21-CCR7 paracrine communication between LECs and GSCs inhibited GSC proliferation and growth. LEC-derived CCL21 induced KAT5-mediated acetylation of HMGCS1 on K273 in GSCs to enhance HMGCS1 protein stability. HMGCS1 promoted cholesterol synthesis in GSCs, favorable for tumor growth. Expression of the CCL21-CCR7 axis correlated with KAT5 expression and HMGCS1K273 acetylation in glioblastoma specimens, informing patient outcome. Collectively, glioblastomas contain previously unrecognized LECs that promote the molecular crosstalk between endothelial and tumor cells, offering potentially alternative therapeutic strategies.

Probing the influence of strontium doping and annealing temperature on the structure and biocompatibility of hydroxyapatite nanorods.

Among numerous biologically important metal cations, strontium (Sr2+) has received much attention in bone tissue regeneration because of its osteoinductive properties combined with its ability to inhibit osteoclast activity. In this study, strontium-doped hydroxyapatite (Sr-HAp) nanorods with varying molar ratios of Ca : Sr (10 : 0, 9 : 1, 5 : 5, 3 : 7 and 0 : 10) were synthesized using the chemical precipitation technique. The synthesized Sr-HAp nanostructures were characterized using powder X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy, energy dispersive X-ray spectroscopy, and Raman and Fourier transform infrared (FTIR) spectroscopies to understand their structural and morphological features, and composition. XRD results revealed the formation of HAp nanostructures, whose unit cell volume increased as a function of the dopant level. The reaction process investigation showed the formation of hydroxyapatite (HAp), strontium apatite (SAp) and various Sr-HAp phases. FESEM micrographs displayed the morphological transformation of Sr-HAp from nanorods to nanosheets upon increasing the dopant level. In the FTIR spectra, the bands of the PO43- group shifted towards a lower wavenumber upon increasing the dopant concentration in Sr-HAp that signifies the structural distortion due to the presence of a large amount of strontium ions. The peaks of PO43- and OH- vibrations in the Raman spectra were further analysed to corroborate the structural distortion of Sr-HAp. Selected area electron diffraction patterns obtained using TEM reveal the reduced crystallinity of Sr-HAp due to Sr-doping, which is in line with the XRD results. Finally, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the synthesized Sr-HAp has no toxic effect on the survival and growth of mesenchymal stem cells. In summary, the synthesized novel Sr-HAp nanorods exhibit great promise for bone tissue engineering applications.

ΔNp63α promotes cigarette smoke-induced renal cancer stem cell activity via the Sonic Hedgehog pathway.

Cigarette smoke (CS) has been generally recognized as a chief carcinogenic factor in renal cell carcinoma (RCC). The stimulative effect of CS on renal cancer stem cells (RCSCs) has been described previously. The Sonic Hedgehog (SHH) pathway plays an essential role in self-renewal, cell growth, drug resistance, metastasis, and recurrence of cancer stem cells (CSCs). Renal cancer-related gene ΔNp63α is highly expressed in renal epithelial tissues and contributes to the RCSCs characteristics of tumors. The aim of this study was to elucidate the role of ΔNp63α and the SHH pathway on the activity of RCSCs induced by CS through a series of in vivo and in vitro studies. It was shown that in renal cancer tissues, ΔNp63α and RCSCs markers in smokers are expressed higher than that in non-smokers. RCSCs were effectively enriched by tumor sphere formation assay. Besides, CS increased the expression of RCSCs markers and the capability of sphere-forming in vitro and in vivo. Moreover, the SHH pathway was activated, and the specialized inhibitor alleviated the promotion of CS on RCSCs. ΔNp63α activated the SHH pathway and promoted CS-induced enhancement of RCSCs activity. These findings indicate that ΔNp63α positively regulates the activity of CS-induced RCSCs via the SHH pathway.