Three thousand years of Hg pollution recorded in mangrove wetland sediments from South China.

Mercury (Hg) is known to affect aquatic, terrestrial ecosystems as well as human health, through biomagnification. Mangrove wetlands are potential Hg sinks because of their low tidal velocity, fast sedimentation rate, strong reducing condition and high organic matter content. The spatial and temporal distribution of Hg has been a hot topic of recent studies in mangrove wetlands. In this study, we investigated Hg concentration, accumulation rate and isotopes to reconstruct the Hg pollution history and to differentiate its potential sources in the Gaoqiao mangrove wetland (Guangdong province), which is part of the largest mangrove area in China. We reconstructed a first, continuous, high-resolution Hg pollution history over the last 3000 years in South China. Our findings show that mangrove wetland sediments are more enriched in Hg than the adjacent grasslands. The increased Hg concentration and δ202Hg in recent sediments mirror the enhanced anthropogenic impacts; Hg concentrations in areas with high levels of anthropogenic disturbance are up to 5× higher than the average background value (9.9 ± 1.2 µg kg-1). Compared to mangroves in coastal areas of South China and around the world, the Hg concentration in Gaoqiao is much lower. The significant increase of Hg since the 1950s and the major Hg peak since the 1980s were the evidence of the human activities influences and indicated the possible start date of Anthropocene. After 2007 CE, a decline in Hg pollution occurs due to the effective implementation of the mangrove protection policy. Three potential sources were identified by the Hg isotope traces including urban gaseous Hg, industrial Hg, and regional soil and leaf litter Hg input.

Motoric Cognitive Risk Syndrome and the Risk of Incident Dementia: A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Epidemiologic studies have indicated an association of motoric cognitive risk syndrome (MCR), a pre-dementia stage characterized by the presence of cognitive complaints and a slow gait, with increased risk of incident dementia. OBJECTIVES: We aimed to clarify this association using meta-analysis. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases up to December 2022 for relevant studies that investigated the association between MCR and incident all-cause dementia and Alzheimer's disease (AD). The random-effects model was used to determine a pooled-effect estimate of the association. RESULTS: We identified seven articles that corresponded with nine cohort studies investigating the association between MCR and the risk of dementia. Pooled analysis showed that MCR was associated with a significantly increased risk of incident all-cause dementia (HR = 2.28; 95% CI: 1.90-2.73) and AD (HR = 2.05; 95% CI: 1.61-2.61). Sensitivity analysis showed that there was no evidence that individual studies influenced the pooled-effect estimate, verifying the robustness of the results. CONCLUSIONS: Our results confirm that MCR is an independent risk factor of incident all-cause dementia and AD. Future studies are needed to better understand the mechanisms underlying this association.

Low concentrations of TNF-α in vitro transform the phenotype of vascular smooth muscle cells and enhance their survival in a three-dimensional culture system.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose challenges. This study aimed to overcome these obstacles using a three-dimensional culture system. METHODS: Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays. RESULTS: TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions. CONCLUSIONS: TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.

Insulin-transferrin-selenium promote formation of tissue-engineered vascular grafts in early stage of culture.

To create tissue-engineered vascular grafts (TEVGs) in vitro, vascular smooth muscle cells (VSMCs) must function effectively and produce sufficient extracellular matrix (ECM) in a three-dimensional space. In this study, we investigated whether the addition of insulin-transferrin-selenium (ITS), a medium supplement, could enhance TEVG formation. PGA fabric was used as the scaffold, and 1% ITS was added to the medium. After two weeks, the tissues were examined using electron microscopy and staining. The ITS group exhibited a denser structure and increased collagen production. VSMCs were cultured in two dimensions with ITS and assessed for collagen production, cell growth, and glucose metabolism. The results showed that ITS supplementation increased collagen production, cell growth, glucose utilization, lactate production, and ATP levels. Furthermore, reducing the amount of fetal bovine serum (FBS) in the medium did not affect the TEVGs or VSMCs when ITS was present. In conclusion, ITS improves TEVG construction by promoting VSMCs growth and reducing the need for FBS.

Vascular Smooth Muscle Cells Mechanosensitive Regulators and Vascular Remodeling.

Blood vessels are subjected to mechanical loads of pressure and flow, inducing smooth muscle circumferential and endothelial shear stresses. The perception and response of vascular tissue and living cells to these stresses and the microenvironment they are exposed to are critical to their function and survival. These mechanical stimuli not only cause morphological changes in cells and vessel walls but also can interfere with biochemical homeostasis, leading to vascular remodeling and dysfunction. However, the mechanisms underlying how these stimuli affect tissue and cellular function, including mechanical stimulation-induced biochemical signaling and mechanical transduction that relies on cytoskeletal integrity, are unclear. This review focuses on signaling pathways that regulate multiple biochemical processes in vascular mesangial smooth muscle cells in response to circumferential stress and are involved in mechanosensitive regulatory molecules in response to mechanotransduction, including ion channels, membrane receptors, integrins, cytoskeletal proteins, nuclear structures, and cascades. Mechanoactivation of these signaling pathways is closely associated with vascular remodeling in physiological or pathophysiological states.

Association between depression and motoric cognitive risk syndrome among community-dwelling older adults in China: A 4-year prospective cohort study.

BACKGROUND AND PURPOSE: Depression can lead to a wide range of adverse health outcomes, including dementia. However, evidence supporting the relationship between depression and motoric cognitive risk syndrome (MCR), a pre-dementia syndrome, remains lacking. This study aimed to examine the association between depression and MCR among community-dwelling Chinese older adults. METHODS: Data were taken from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Depression was defined by a Center for Epidemiological Studies Depression Scale (CES-D) score ≥10. MCR was defined as subjective cognitive complaints and objective slow gait speed. Multivariate logistic regression analyses were conducted to examine the cross-sectional and longitudinal associations between depression and MCR at baseline and a 4-year follow-up period for the sample population and gender groups. RESULTS: The prevalence of MCR was higher in participants with depression than in those without depression at baseline (12.2% vs. 8.9%; p = 0.001). Participants with depression at baseline had a higher 4-year incidence of MCR than those without depression (14.8% vs. 8.7%; p < 0.001). Both cross-sectional analysis (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.13-1.75) and prospective analysis (OR 1.95, 95% CI 1.56-2.44) demonstrated that depression was significantly associated with MCR. These associations were consistent across different gender groups and stronger among female individuals. CONCLUSIONS: Depression is an independent risk factor for MCR among community-dwelling Chinese older adults. Special attention should be paid to the care of older people with depression to reduce the occurrence of MCR and even dementia.

Hybrid ablation procedure for the treatment of nonparoxysmal atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Hybrid ablation combines the advantages of surgical and catheter ablation. Many studies have explored the efficiency and safety of hybrid ablation in patients with nonparoxysmal AF. METHODS: We systematically searched for prospective controlled trials that compared hybrid ablation with catheter/surgical ablation in PubMed, Web of Science, Wiley Library, and CNKI. Our main assessment indicators included maintenance of sinus rhythm (SR) without antiarrhythmic drugs for more than 12 months, major adverse events (MAEs), procedure time and fluoroscopy time. RESULTS: Of 1214 identified studies, five were eligible and were included in our analysis (N = 451 participants). The pooled results showed that hybrid ablation was more effective in maintaining SR than a single procedure (surgical ablation or catheter ablation) (OR = 2.52, 95% confidence interval [CI]: 1.63-3.89, p < .001). Little significant heterogeneity was revealed (p = .32 for heterogeneity, I2  = 14%). More MAEs occurred in the hybrid group than in the single procedure group (OR = 7.47, 95% CI: 1.90-29.41, p = .004; I2  = 0%). Two trials reported the procedure and fluoroscopy times, and the procedure time for hybrid ablation was significantly longer than that of a single procedure (mean difference = 107.42, 95% CI: 88.62 to 126.22, p < .001; I2  = 82%). There was no significant difference in fluoroscopy time between the 2 groups (mean difference = -1.00, 95% CI: -5.37 to 3.36, p = .65; I2  = 12%). CONCLUSIONS: Hybrid ablation was more effective than catheter ablation and was as effective as surgical ablation in patients with nonparoxysmal AF. Meanwhile, hybrid ablation, especially concomitant hybrid ablation, increases the incidence of MAEs and prolongs the procedure time.

A Novel Preparation Method for Effervescent Tablets of Xianganfang Containing Fresh Juice using a Semi-Solid Extrusion 3D Printer with Three Cartridge Holders.

This study aimed to prepare effervescent tablets of traditional Chinese medicine Xianganfang with fresh juice using a semi-solid 3D printer with three cartridge holders to seperate acid and alkali source by drug paste through model design to avoid sticking impact and premature effervescence during the tableting in the conventional preparation process. The powder of Xianganfang including fresh juice of Phyllanthus emblica and licorice extract was obtained by vacuum freeze-drying with 50% mannitol as cryoprotectant. Then, the formulation of 3D-printed effervescent tablets was investigated. Further 5% HPMC hydroalcoholic gel was mixed with sodium bicarbonate and freeze-dried Xianganfang powder to prepare alkali source and drug paste respectively while 30% PVP ethanol solution was mixed with tartaric acid to prepare acid source paste; these three pastes had good printability. The pastes of drug, acid, and alkali were loaded into three syringe cartridges separately and numbered as "3," "5," and "7," according to cartridge holders of the 3D printer, and printed in the order of "537,353,735" for separating acid and alkali by drug to avoid premature effervescence. And the basic printing parameters were optimized. The tablets were evaluated by the appearance, tablet weight variation, hardness, disintegration time, friability, pH, and stability. The physicochemical properties all conformed to the Chinese Pharmacopoeia 2020 edition. The content of the active ingredient gallic acid was 0.769 ± 0.019 mg/g. This study provided a new method to prepare effervescent tablets of traditional Chinese medicine with fresh juice using 3D printing technology.

Intravital confocal fluorescence lifetime imaging microscopy in the second near-infrared window.

We present confocal fluorescence lifetime imaging microscopy in the second near-infrared (NIR-II) window to assess the morphological and biochemical information of live samples. A home-built superconducting single-photon detector (SSPD) was used to facilitate the NIR-II fluorescence lifetime measurement. The SSPD has many advantages, including high sensitivity to NIR-II signals (detection efficiency >50%), fast temporal response (∼109ps), low timing jitter (∼50ps), and low dark count rate (<100cps). We demonstrate the feasibility of the developed microscopy system by comparing fluorescence lifetimes of a range of fluorophores with emission in the NIR-II window and by performing multicolor three-dimensional fluorescence lifetime imaging of a mouse ear in vivo. The biochemical properties of the cells and tissues probed by the fluorescence lifetimes of the fluorophores provide complementary information for biomedical studies, significantly benefiting diverse applications in life science.

Prediction of Catch-Slip Bond Transition of Kindlin2/ß3 Integrin via Steered Molecular Dynamics Simulation.

Kindlin2 is believed to be crucial in integrin activation, which mediates the cell-extracellular matrix adhesion and signaling, but the mechanoregulation of the interaction between Kindlin2 and integrin remains unclear. Here, we performed the so-called "ramp-clamp" steered molecular dynamics simulation on the crystal structure of Kindlin2 bound with ß3 integrin. The results showed that the complex had a better mechanical strength for its rupture force of about 200 pN under pulling with the velocity of 1 Å/ns, and was mechanostable for its conformational conservation under constant tensile force (≤60 pN). The catch-slip bond transition with a force threshold of 20 pN was demonstrated by the dissociation probability, the interaction energy, the interface H-bond number, and the force-induced allostery of the complex. This study might provide a novel insight into force-dependent Kindlin2/integrin-related signaling and its structural basis in cellular processes as well as a rational SMD-based computer strategy for predicting the structure-function relationship of the stretched complex.

In vitro remodeling and structural characterization of degradable polymer scaffold-based tissue-engineered vascular grafts using optical coherence tomography.

Non-destructive imaging strategies to monitor long-term cultures is essential for vascular engineering. The goal of this study is to investigate whether optical coherence tomography (OCT) can be a suitable approach to monitor the long-term remodeling process of biodegradable polymeric scaffold-based tissue-engineered vascular grafts (TEVG) after pulsatile stimulation and to observe polymeric scaffold degradation during bioreactor cultivation. In the present study, a perfusion system driven by a ventricular assist device was provided for a three-dimensional culture system as a pulsatile force. We characterized the structural features of wall thickness and polyglycolic acid degradation based on optical signal attenuation using catheter-based OCT. Scanning electron microscopy confirmed morphological changes. Also, polymer degradation and the detection of different types of collagen was visualized after 4 weeks of culture by means of polarized microscopy. Findings on OCT imaging correlated with those on histological examination and revealed the effects of pulsatile stimulation on the development of engineered vessels. This finding demonstrated that real-time imaging with OCT may be a promising tool for monitoring the growth and remodeling characterization of TEVG and provide a basis to promote the ideal and long-term culture of vascular tissue engineering.

PEG 300 Promotes Mesodermal Differentiation in iPSC-Derived Embryoid Body Formation In Vitro.

Embryoid bodies (EB) are sensitive to changes in the culture conditions. Recent studies show that the addition of PEG 300 to culture medium affects cell growth and differentiation; however, its effect on the embryoid body is unclear. This study aims to understand the role of PEG 300 in the process of EB formation and germ layer differentiation. EBs formed more efficiently and differentiated toward the mesoderm when cultured in a medium supplemented with appropriate concentrations of PEG 300. The expression of T/Bry, a marker of mesodermal differentiation, increases in EBs in the PEG group, and the expression of TUBB3 generally decreases, showing a quantitative relationship with PEG. Furthermore, further differentiation of PEG-pretreated EB into vascular smooth muscle cells (VSMCs) by directional induction shows that PEG 300-pretreated induced VSMCs have higher expression of phenotypic markers and greater secretory and contractile functions. This study highlights the role of PEG 300 in the culture medium during EB differentiation, which can significantly enhance mesodermal gene expression and the efficiency of subsequent differentiation into smooth muscle cells and other target cells.

Macromolecular Crowding Enhances Matrix Protein Deposition in Tissue-Engineered Vascular Grafts.

Successful in vitro culture of small-diameter tissue-engineered vascular grafts (TEVGs) requires rapid deposition of biomacromolecules secreted by vascular smooth muscle cells in a polyglycolic acid mesh scaffold's three-dimensional (3D) porous environment. However, common media have lower crowding conditions than in vivo tissue fluids. In addition, during the early stages of construction, most of the biomolecules secreted by the cells into the medium are lost, which negatively affects the TEVG culture process. In this study, we propose the use of macromolecular crowding (MMC) to enhance medium crowding to improve the deposition and self-assembly efficiency of major biomolecules in the early stages of TEVG culture. The addition of carrageenan significantly increased the degree of MMC in the culture medium without affecting cell viability, proliferation, and metabolic activity. Protein analysis demonstrated that the deposition of collagen types I and III and fibronectin increased significantly in the cell layers of two-dimensional and 3D smooth muscle cell cultures after the addition of a MMC agent. Collagen type I in the culture medium decreased significantly compared with that in the medium without a MMC agent. Scanning electron microscopy demonstrated that MMC agents considerably enhanced the formation of matrix protein structures during the early stages of 3D culture. Hence, MMC modifies the crowding degree of the culture medium, resulting in the rapid formation of numerous matrix proteins and fiber structures. Impact Statement Small-diameter tissue-engineered vascular grafts (TEVGs) are one of the most promising means of treating cardiovascular diseases; however, the in vitro construction of TEVGs has some limitations, such as slow deposition of extracellular matrix (ECM), long culture period, and poor mechanical properties. We hypothesized that macromolecular crowding can increase the crowding of the culture medium to construct a more bionic microenvironment, which enhances ECM deposition in the medium to the cell layer and reduces collagen loss, accelerating and enhancing TEVG culture and construction in vitro.

Carrageenan maintains the contractile phenotype of vascular smooth muscle cells by increasing macromolecular crowding in vitro.

BACKGROUND: The contractile phenotype of vascular smooth muscle cells (VSMCs) results in good diastolic and contractile capacities, and its altered function is the main pathophysiological basis for diseases such as hypertension. VSMCs exist as a synthetic phenotype in vitro, making it challenging to maintain a contractile phenotype for research. It is widely recognized that the common medium in vitro is significantly less crowded than in the in vivo environment. Additionally, VSMCs have a heightened sense for detecting changes in medium crowding. However, it is unclear whether macromolecular crowding (MMC) helps maintain the VSMCs contractile phenotype. PURPOSE: This study aimed to explore the phenotypic, behavioral and gene expression changes of VSMCs after increasing the crowding degree by adding carrageenan (CR). METHODS: The degree of medium crowding was examined by a dynamic light scattering assay; VSMCs survival and activity were examined by calcein/PI cell activity and toxicity and CCK-8 assays; VSMCs phenotypes and migration were examined by WB and wound healing assays; and gene expression was examined by transcriptomic analysis and RT-qPCR. RESULTS: Notably, 225 µg/mL CR significantly increased the crowding degree of the medium and did not affect cell survival. Simultaneously, CR significantly promoted the contraction phenotypic marker expression in VSMCs, shortened cell length, decreased cell proliferation, and inhibited cell migration. CR significantly altered gene expression in VSMCs. Specifically, 856 genes were upregulated and 1207 genes were downregulated. These alterations primarily affect the cellular ion channel transport, microtubule movement, respiratory metabolism, amino acid transport, and extracellular matrix synthesis. The upregulated genes were primarily involved in the cytoskeleton and contraction processes of VSMCs, whereas the downregulated genes were mainly involved in extracellular matrix synthesis. CONCLUSIONS: The in vitro study showed that VSMCs can maintain the contractile phenotype by sensing changes in the crowding of the culture environment, which can be maintained by adding CR.

Dietary patterns from mid-through later-life in relation to sarcopenia risk over 20 years among Chinese community-dwelling oldest old individuals.

BACKGROUND: Evidence regarding how dietary patterns (DPs) from mid- (60 years old) to later-life (over 80 years old) affect sarcopenia risk in old age is scarce. METHODS: We included 7267 participants aged ≥80 years from the Chinese Longitudinal Healthy Longevity Survey in 2018. The Simplified Healthy Eating Index (SHE index) based on nine dietary variables was used to measured DPs and changes in DPs, with a higher score indicating better diet quality. The term "Mid-life" DPs denoted dietary habits at the age of 60 whereas "Later-life" DPs referred to dietary habits acquired over 80 years old. Sarcopenia risk was evaluated using the SARC-CalF questionnaire. We applied multivariable adjusted logistic regression models to investigate the cross-sectional association between DPs in a life course and sarcopenia risk in 2018 after adjusting for potential confounders including sociodemographic characteristics, lifestyle risk factors, and unfavorable health conditions. Several sensitivity analyses were conducted to verify the robustness of the results. RESULTS: We found that healthier DPs during both mid- and later-life were associated with a decreased odds of sarcopenia risk, with adjusted odds ratios (ORs) of 0.69 (95 % confidence interval [CI]: 0.54-0.88) and 0.84 (95 % CI: 0.71-0.99), respectively. The odds of sarcopenia risk were also decreased among those with healthier DPs over a period of 20 years (OR = 0.80, 95 % CI: 0.69-0.93). For each nutrient consumption, participants who had high-quality fish consumption both in mid- and later-life had a 23 % decreased odds of sarcopenia risk (OR = 0.77, 95 % CI: 0.67-0.88) compared with those who had low-quality fish consumption all the time. The results were largely unchanged in sensitivity analyses. CONCLUSIONS: Our findings highlight the importance of maintaining healthy dietary habits throughout life to reduce the risk of sarcopenia in old age.

PRP significantly promotes the adhesion and migration of vascular smooth muscle cells on stent material.

BACKGROUND: The adhesion and survival state of cells on scaffold material is a major problem in tissue-engineered blood vessel (TEBV) culture. Platelet-rich plasma (PRP) contains a large amount of biologically active factors and fibrin, which is expected to play an important role in TEBV culture. PURPOSE: To combine PRP with cells and scaffold material to promote cell adhesion and biological activity on the scaffold material. METHODS: The adhesion status and migration of SMCs under the optimal concentration suitable for SMC growth and the optimal concentration of PRP were examined by scanning electron microscopy, HE staining, CCK-8 assays, qPCR, WB, and other experimental methods and compared with those under the conventional culture (20% FBS); finally, the effect of PRP on the deposition of ECM in vascular tissue engineering culture was verified by three-dimensional culture. RESULTS: PRP at 20% is a suitable concentration for SMCs. Compared with the control group, the 20% PRP group had better migration, and the number of SMC adhesions was significantly higher than that of the control group. In addition, collagen deposition in the experimental group was significantly higher than that in the control group. CONCLUSION: PRP (20%) can promote SMC adhesion, migration, and collagen deposition on the scaffold material.

Prevalence and Correlates of Motoric Cognitive Risk Syndrome in Chinese Community-Dwelling Older Adults.

Background: Motoric cognitive risk (MCR) syndrome is considered to be a pre-dementia syndrome. Although an increasing number of studies have begun to focus on this syndrome, few investigations have been launched in China. This study was performed to examine the prevalence and correlates of MCR in China. Methods: We included 5,725 adults aged over 60 years from China Health and Retirement Longitudinal Study (CHARLS). MCR was defined as the presence of subjective cognitive complaints and a gait speed ≤20th percentile of the weighted population distribution adjusted for sex and height. The associations among selected modifiable associated factors and clinical measures with MCR were examined using multivariate logistic regression analysis. Results: Of the participants, 414 met the criteria for MCR with an overall prevalence 7.29% (95% CI: 6.62-7.96%). MCR was found to be more prevalent among women than men (9.73 vs 4.85%), and more prevalent among participants ≥75 years than those <75 years (7.85 vs 5.23%). After multivariable adjustment, lower or upper extremity functional limitations, activities of daily living (ADL) disabilities, weak grip strength, exhaustion, and history of hypertension were found to be significantly associated with MCR. The multivariate analysis also showed higher levels of cystatin C and C-reactive protein were associated with increased odds for MCR. Conclusions: The present study showed that MCR syndrome is highly prevalent among Chinese community-dwelling older adults, and revealed several factors that were correlated with MCR. Longitudinal studies are warranted to further explore the modifiable risk factors of MCR.

Motoric cognitive risk syndrome as a predictor of incident disability: A 7 year follow-up study.

Background: Though motoric cognitive risk syndrome (MCR) share risk factors with disability, whether it predict disability remains understudied. Objectives: This study aims to examine the association between MCR and incident disability. Design: Longitudinal study. Methods: MCR was defined as subjective cognitive complaints and objective slow gait speed. Two subtypes of MCR were defined by whether memory impairment (MI) was also present, MCR-MI and MCR-non-MI. Incident activities of daily living (ADL) disability and instrumental activities of daily living (IADL) disability were outcome measures. Multiple logistic regression analysis was used to assess the independent effect of MCR at baseline on the odds of ADL/IADL disability at a 7 year follow-up. Results: Among the subjects who were not disabled at baseline and followed for 7 years, 34.66% reported incident ADL disability, and 31.64% reported incident IADL disability. Compared with participants without MCR at baseline, those with MCR had 58% increased odds of incident ADL disability (OR=1.58, 95% CI: 1.19-2.09) and 46% increased odds of incident IADL disability (OR=1.46, 95% CI: 1.13-1.88) after 7 years. MCR-non-MI was associated with a 56.63% increased risk of ADL disability and a 34.73% increased risk of IADL disability. MCR-MI was associated with an even higher risk of IADL disability (OR = 2.14, 95% CI: 1.18-3.88). Conclusions: MCR is an independent risk factor for both incident ADL and IADL disability. MCR-MI predicts a higher risk for disability than MCR-non-MI. Early identification of MCR among older adult is recommended and may decrease future risk of disability.

Hypoxia facilitates proliferation of smooth muscle cells derived from pluripotent stem cells for vascular tissue engineering.

Tissue-engineered blood vessels (TEBVs) show significant therapeutic potential for replacing diseased blood vessels. Vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (hiPSCs) via embryoid body (EB)-based differentiation, are promising seed cells to construct TEBVs. However, obtaining sufficient high-quality hiPSC-VSMCs remains challenging. Stem cells are located in a niche characterized by hypoxia. Hence, we explored molecular and cellular functions at different induction stages from the EB formation commencement to the end of directed differentiation under normoxic and hypoxic conditions, respectively. Hypoxia enhanced the formation, adhesion and amplification rates of EBs. During directed differentiation, hiPSC-VSMCs exhibited increased cell viability under hypoxic conditions. Moreover, seeding hypoxia-pretreated cells on biodegradable scaffolds, facilitated collagen I and elastin secretion, which has significant application value for TEBV development. Hence, we proposed that hypoxic treatment during differentiation effectively induces proliferative hiPSC-VSMCs, expanding high-quality seed cell sources for TEBV construction.

Corrigendum: Micro-Nano Bioactive Glass Particles Incorporated Porous Scaffold for Promoting Osteogenesis and Angiogenesis in vitro.

[This corrects the article DOI: 10.3389/fchem.2019.00186.].