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Gene therapy involves replacing a faulty gene or adding a new gene inside the body's cells to cure disease or improve the body's ability to fight disease. Its popularity is evident from emerging concepts such as CRISPR-based genome editing and epigenetic studies and has been moved to a clinical setting. The strategy for therapeutic gene design includes; suppressing the expression of pathogenic genes, enhancing necessary protein production, and stimulating the immune system, which can be incorporated into both viral and non-viral gene vectors. Although non-viral gene delivery provides a safer platform, it suffers from an inefficient rate of gene transfection, which means a few genes could be successfully transfected and expressed within the cells. Incorporating nucleic acids into the viruses and using these viral vectors to infect cells increases gene transfection efficiency. Consequently, more cells will respond, more genes will be expressed, and sustained and successful gene therapy can be achieved. Combining nanoparticles (NPs) and nucleic acids protects genetic materials from enzymatic degradation. Furthermore, the vectors can be transferred faster, facilitating cell attachment and cellular uptake. Magnetically assisted viral transduction (magnetofection) enhances gene therapy efficiency by mixing magnetic nanoparticles (MNPs) with gene vectors and exerting a magnetic field to guide a significant number of vectors directly onto the cells. This research critically reviews the MNPs and the physiochemical properties needed to assemble an appropriate magnetic viral vector, discussing cellular hurdles and attitudes toward overcoming these barriers to reach clinical gene therapy perspectives. We focus on the studies conducted on the various applications of magnetic viral vectors in cancer therapies, regenerative medicine, tissue engineering, cell sorting, and virus isolation.
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Ácidos Nucleicos , Vírus , Transfecção , Vetores Genéticos/genética , Técnicas de Transferência de Genes , Ácidos Nucleicos/genética , Vírus/genéticaRESUMO
Damage to the spinal cord triggers a local complex inflammatory reaction that results in irreversible impairments or complete loss of motor function. The evidence suggested that inhibiting the pro-inflammatory macrophage/microglia (M1 subsets) and stimulating the anti-inflammatory macrophage/microglia (M2 subsets) are potential strategies for the treatment of neuroinflammation-related diseases. We evaluated the potentially protective effect of Ac-SDKP as an endogenous tetrapeptide on rat spinal cord injury (SCI). Wistar rats were subjected to a weight-drop contusion model and were treated with Ac-SDKP (0.8 mg/kg) given subcutaneously once a day for 7 days starting at two clinically relevant times, at 2 h or 6 h post-injury. The effect of Ac-SDKP was assessed by motor functional analysis, real-time PCR (CD86 and CD206 mRNA), western blot (caspase-3), ELISA (TNF-a, IL-10), and histological analysis (toluidine blue staining). Ac-SDKP improved locomotor recovery and rescue motor neuron loss after SCI. Moreover, a decreased in TNF-a level as well as caspase 3 protein levels occurred in the lesion epicenter of the spinal cord following treatment. In addition, CD206 mRNA expression level increased significantly in Ac-SDKP treated rats compared with SCI. Together these data suggest that Ac-SDKP might be a novel immunomodulatory drug. It may be beneficial for the treatment of SCI with regards to increasing CD206 gene expression and suppress inflammatory cytokine to improve motor function and reducing histopathological lesion.
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Traumatismos da Medula Espinal , Animais , Oligopeptídeos/farmacologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismoRESUMO
The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.
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COVID-19 , Transtornos do Olfato , Anosmia , COVID-19/complicações , Humanos , SARS-CoV-2 , Olfato , Síndrome de COVID-19 Pós-AgudaRESUMO
COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.
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Adenocarcinoma/etiologia , COVID-19/complicações , Carcinogênese/genética , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Neoplasias Pancreáticas/etiologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/complicações , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , COVID-19/genética , COVID-19/metabolismo , COVID-19/virologia , Caspase 3/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Influenza Humana/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , PTEN Fosfo-Hidrolase/genética , Mapas de Interação de Proteínas , Risco , Síndrome Respiratória Aguda Grave/genética , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais/genética , Proteína Smad3/genética , Regulação para Cima/genéticaRESUMO
Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries.
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In this study, the effects of various parameters of the water-in-oil emulsification/internal gelation method on the properties of calcium-alginate microparticles were evaluated and optimized. Results showed that the spherical-shaped microparticles with the highest circularity and high production yield can be produced by alginate solution with a concentration of 2 wt.%, calcium carbonate/alginate ratio of 10/1 (w/w), water/oil volume ratio of 1/20, emulsifier concentration of 5 % (v/v), and emulsification speed of 1000 rpm. Two model drugs including simvastatin lactone and simvastatin ß-hydroxyacid were loaded into the microspheres with promising encapsulation efficiencies of 73 % and 69 %, respectively. The microspheres showed a pH-responsive swelling behavior with a percentage of 10.60 %, 352.65 %, 690.03 %, and 1211.46 % at the pH values of 2.0, 4.5, 7.4, and 8.5, respectively. The microspheres showed an increasing trend of release rate in direct proportion to pH. These findings would be useful for therapeutic applications which need pH-responsive drug carriers.
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Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE-approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps > 30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.
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For nearly two decades, coronaviruses have caused many health and economic problems, while no effective commercial vaccine has yet been developed. It is worth mentioning that despite some mutations and recombination in SARS-CoV-2, its genotype is very close to the original strain from Wuhan, China. Therefore, the development of an effective vaccine would be promising. It might be hypothesized that BCG vaccination is performed in high-risk populations before the commercialization of an effective SARS-CoV-2 vaccine. However, the development of an effective vaccine without considering the adverse immune reactions derived from antibody-dependent or cell-based immune enhancement may threaten vaccinated people's lives and long-term side effects must be considered. To this end, targeting of the receptor-binding domain (RBD) in spike and not whole spike, glycolization of FC receptors, PD-1 blockers, CPPs, etc., are promising. Therefore, the subunit vaccines or RNA vaccines that encode the RBP segment of the spike are of interest. To enhance the vaccine efficacy, its co-delivery with an adjuvant has been recommended. Nanoparticles modulate immune response with higher efficiency than the soluble form of antigens and can be functionalized with the positively charged moieties and ligands of targeted cells, such as dendritic cells, to increase cellular uptake of the antigens and their presentation on the surface of immune cells. This research aimed to discuss the COVID-19 vaccines entering the clinical trial and their mode of action effective immunity against the virus and discusses their advantages compared to each other.
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COVID-19 , Vacinas Virais , Vacinas contra COVID-19 , China , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
Engineering of 3D substrates with maximum similarity to seminiferous tubules would help to produce functional sperm cells in vitro from stem cells. Here, we present a 3D electrospun gelatin (EG) substrate seeded with Sertoli cells and determine its potential for guided differentiation of embryonic stem cells (ESCs) toward germline cells. The EG was fabricated by electrospinning, and its morphology under SEM, as well as cytobiocompatibility for Sertoli cells and ESCs, was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and cell attachment assay. Embryoid bodies (EBs) were formed from ESCs and co-cultured with Sertoli cells, induced with BMP4 for 3 and 7 consecutive days to induce the differentiation of EBs toward germline cells. The differentiation was investigated by immunocytochemistry (ICC), flow cytometry, and RT-PCR in four experimental groups of EBs (EBs cultured in gelatin-coated cell culture plates); Scaffold/EB (EBs cultured on EG); ESCs/Ser (EBs and Sertoli cells co-cultured on gelatin-coated cell culture plates without EG); and Scaffold/EB/Ser (EBs and Sertoli cells co-cultured on EG). All experimental groups exhibited a significantly increased MVH (germline-specific marker) and decreased c-KIT (stemness marker) expression when compared with the EB group. ICC and flow cytometry revealed that Scaffold/EB/Ser had the highest level of MVH and the lowest c-KIT expression at both 3 and 7 days postdifferentiation compared with other groups. RT-PCR results showed a significant increase in the germline marker (Dazl) and a significant decrease in the ESC stemness marker (Nanog) in Scaffold/EB compared to the EB group. The germline markers Gcna, Stella, Mvh, Stra8, Piwil2, and Dazl were significantly increased in Scaffold/EB/Ser compared to the Scaffold/EB group. Our findings revealed that the EG scaffold can provide an excellent substrate biomimicking the micro/nanostructure of native seminiferous tubules and a platform for Sertoli cell-EB communication required for growth and differentiation of ESCs into germline cells.
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Células-Tronco Embrionárias , Gelatina , Células Cultivadas , Técnicas de Cocultura , Masculino , EspermatozoidesRESUMO
Treatment of non-healing skin wounds infected with extensively drug-resistant (XDR) bacteria remains as a big challenge. To date, different biomaterials have been applied for treatment of post-wound infections, nevertheless their efficacy for treatment of the wounds infected with XDR isolates has not been determined yet. In this study, the potential of the thermo-responsive chitosan (TCTS) hydrogel for protection of full-thickness wounds XDR bacteria isolated from burn patients was evaluated both in vitro and in vivo in a rat model. Antibacterial activity of the TCTS hydrogel against standard strain and clinical isolates of Acinetobacter baumannii, cytobiocompatibility for Hu02 fibroblast cells, degradation rate and swelling ratio were determined in vitro. MTT assay and disk diffusion test indicated no detectable cytotoxicity and antibacterial activity in vitro, respectively. In vivo study showed significant acceleration of wound healing, re-epithelialization, wound closure, and decreased colony count in the TCTS hydrogel group compared with control. This study suggests TCTS hydrogel as an excellent wound dressing for management of the wounds infected with XDR bacteria, and now promises to proceed with clinical investigations.
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Infecções por Acinetobacter/terapia , Acinetobacter baumannii/efeitos dos fármacos , Curativos Hidrocoloides , Queimaduras/microbiologia , Quitosana , Farmacorresistência Bacteriana Múltipla , Hidrogéis/uso terapêutico , Cicatrização , Infecção dos Ferimentos/terapia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Animais , Carga Bacteriana , Adesão Celular , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Estabilidade de Medicamentos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Teste de Materiais , Ratos , Ratos Sprague-Dawley , Infecção dos Ferimentos/microbiologiaRESUMO
OBJECTIVES: The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation. METHODS: Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10-15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years. RESULTS: Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications. CONCLUSIONS: Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.
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Procedimentos Cirúrgicos Cardíacos , Quilotórax , Plasma Rico em Plaquetas , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Quilotórax/etiologia , Quilotórax/cirurgia , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , ReoperaçãoRESUMO
Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name "Hastalex" in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX.
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Materiais Biocompatíveis , Grafite , Próteses Valvulares Cardíacas , Nanocompostos , Poliuretanos , Células A549 , Animais , Materiais Biocompatíveis/toxicidade , Calcinose/induzido quimicamente , Bovinos , Módulo de Elasticidade , Grafite/toxicidade , Hemólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Hibridomas/efeitos dos fármacos , Teste de Materiais , Microscopia Eletrônica de Varredura , Nanocompostos/toxicidade , Nanocompostos/ultraestrutura , Pericárdio , Adesividade Plaquetária/efeitos dos fármacos , Polímeros/toxicidade , Politetrafluoretileno/toxicidade , Poliuretanos/toxicidade , Desenho de Prótese , Ratos , Ratos Wistar , Propriedades de Superfície , Resistência à TraçãoRESUMO
Despite the abundance of skin substitutes in the worldwide market, major hurdles in developing more complex tissues include the addition of skin appendages and vascular networks as the most important structure. The aim of this research was a clinical feasibility study of a novel prevascularized skin grafts containing the dermal and epidermal layer using the adipose stromal vascular fraction (SVF)-derived endothelial cell population for vascular network regeneration. Herein, we characterized hydrogel with emphasis on biological compatibility and cell proliferation, migration, and vitality. The therapeutic potential of the prevascularized hydrogel transplanted on five human subjects as an intervention group with diabetic wounds was compared with nonvascularized skin grafts as the control on five patients. Wound planimetric and biometric analysis was performed using a Mann-Whitney nonparametric t-test (p ≤ .05). The fibrin-collagen hydrogel was suitable for skin organotypic cell culture. There was a significant (p ≤ .05) increased in skin thickness and density in the vascular beds of the hypodermis measured with skin scanner compared with that in the control group. No significant macroscopic differences were observed between the intervention and control groups (p ≤ .05). In summary, we report for the first time the use of autologous dermal-epidermal skin grafts with intrinsic vascular plexus in a clinical feasibility study. The preliminary data showed that SVF-based full-thickness skin grafts are safe and accelerate the wound healing process. The next stage of the study is a full-scale randomized clinical trial for the treatment of patients with chronic wounds.
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Pé Diabético , Hidrogéis , Transplante de Pele , Pele Artificial , Pele , Engenharia Tecidual , Adulto , Idoso , Colágeno/administração & dosagem , Colágeno/química , Pé Diabético/metabolismo , Pé Diabético/patologia , Pé Diabético/cirurgia , Feminino , Fibrina/administração & dosagem , Fibrina/química , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/química , Masculino , Pessoa de Meia-Idade , Pele/metabolismo , Pele/patologiaRESUMO
In the last decade, the Islamic Republic of Iran has witnessed significant improvement and growth in the field of interdisciplinary medicine and in its translation to patients, including the field of cell and stem cell therapy. The main aim of this report is to highlight various advances in regenerative medicine for skin and dermatology using stem cell technology, and its translation to clinic in the past two decades, in Iranian academic centers, clinical institutes and hospitals. While there have been numerous positive advances in clinical outcomes reported in Iran, there is no comparative analytical information on these studies. Here we present a historical overview of the progress and key advancements seen in skin regeneration in this country, review the research frameworks, regulatory approach and pathways and offer perspectives for the future.
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Medicina Regenerativa , Pele/patologia , Ensaios Clínicos como Assunto , História do Século XXI , Humanos , Irã (Geográfico) , Publicações , Medicina Regenerativa/história , Engenharia TecidualRESUMO
An ultra-low percolation threshold electrically conductive polymer nanocomposite incorporating graphene into a polyhedral oligomeric silsesquioxane polycaprolactone (POSS-PCL/graphene) is described in this paper. Multilayer graphene flakes were homogeneously dispersed into POSS-PCL at 0.08, 0.4, 0.8, 1.6, and 4.0â¯wt% concentrations. The impedance spectroscopy of 0.08â¯wt% and higher concentration of graphene in POSS-PCL represented major improvement in conductivity over pristine POSS-PCL. The percolation threshold occurred at 0.08â¯wt% graphene concentration, and at 4.0â¯wt% the electrical conductivity exceeded 10-4 Scm-1. Furthermore, the chemical, morphological, and mechanical of the POSS-PCL/graphene with various graphene concentrations were investigated. Finally, neural cells cultured on all POSS-PCL/graphene constructs indicated higher metabolic activity and cell proliferation in comparison with pristine POSS-PCL. Herein, we demonstrate a method of developing a neural-compatible and electrically conductive polymer nanocomposite that could potentially function as a neural tissue engineered platform technology for neurological and neurosurgical applications.
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Condutividade Elétrica , Grafite/química , Nanocompostos/química , Tecido Nervoso/fisiologia , Neurocirurgia , Poliésteres/química , Engenharia Tecidual/métodos , Animais , Proliferação de Células , Sobrevivência Celular , DNA/metabolismo , Compostos de Organossilício/química , Espectroscopia Fotoeletrônica , Ratos Wistar , Células de Schwann/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Propriedades de Superfície , Resistência à TraçãoRESUMO
Bone and cartilage craniofacial defects due to trauma or congenital deformities pose a difficult problem for reconstructive surgeons. Human adipose stem cells (ADSCs) can differentiate into bone and cartilage and together with suitable scaffolds could provide a promising system for skeletal tissue engineering. It has been suggested that nanomaterials can direct cell behavior depending on their surface nanotopographies. Thus, this study examined whether by altering a nanoscaffold surface using radiofrequency to excite gases, argon (Ar), nitrogen (N2) and oxygen (O2) with a single step technique, we could enhance the osteogenic and chondrogenic potential of ADSCs. At 24â¯h, Ar modification promoted the highest increase in ADSCs adhesion as indicated by upregulation of vinculin and focal adhesion kinase (FAK) expression compared to O2 and N2 scaffolds. Furthermore, ADSCs on Ar-modified nanocomposite polymer POSS-PCU scaffolds upregulated expression of bone markers, alkaline phosphatase, collagen I and osteocalcin after 3â¯weeks. Cartilage markers, aggrecan and collagen II, were also upregulated on Ar-modified scaffolds at the mRNA and protein level. Finally, all plasma treated scaffolds supported tissue ingrowth and angiogenesis after grafting onto the chick chorioallantoic membrane. Ar promoted greater expression of vascular endothelial growth factor and laminin in ovo compared to O2 and N2 scaffolds as shown by immunohistochemistry. This study provides an important understanding into which surface chemistries best support the osteogenic and chondrogenic differentiation of ADSCs that could be harnessed for regenerative skeletal applications. Argon surface modification is a simple tool that can promote ADSC skeletal differentiation that is easily amenable to translation into clinical practice.
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Tecido Adiposo/metabolismo , Argônio/química , Diferenciação Celular , Condrogênese , Nanocompostos/química , Osteogênese , Gases em Plasma/química , Poliuretanos/química , Células-Tronco/metabolismo , Engenharia Tecidual , Alicerces Teciduais/química , Tecido Adiposo/citologia , Células Cultivadas , Humanos , Células-Tronco/citologiaRESUMO
Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC-specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients.
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Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Exossomos/genética , MicroRNAs/genética , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , HumanosRESUMO
The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.
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Tecido Adiposo/citologia , Medicina Regenerativa , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Engenharia Tecidual/métodos , Animais , Diferenciação Celular , HumanosRESUMO
An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices.