RESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After publication, the Editors were contacted by a concerned reader regarding alleged image duplication. These allegations are in regard to Fig. 3a being duplicated from a previously published paper in the journal Stem Cells (Stem Cells. 2008 Sep;26 (9):2332-8. doi: 10.1634/stemcells.2008-0084) and Fig. 8a being duplicated from a previously published paper in the journal Molecular Cancer (Mol Cancer 13, 255 (2014). https://doi.org/10.1186/1476-4598-13-255). After a thorough investigation by the editorial team, the Editors determined that there are multiple identical details between Fig. 5A (Cancer Letters) and Fig. 3A (Stem Cells) and the authors did not produce satisfactory evidence that the published images in Cancer Letters were original. Due to this, the Editor does not have confidence in the results and conclusions presented and has made the decision to retract.
RESUMEN
Regarding their reversible damage of insulin-producing cells (IPCs) and the inefficiency of treatment methods for type 1 diabetes mellitus (T1DM), scientists decided to produce IPCs from an unlimited source of cells. But the production of these cells is constantly faced with problems such as low differentiation efficiency in cell therapy and regenerative medicine. This study provided an ideal differentiation medium enriched with plasma-rich platelet (PRP) delivery to produce IPCs from menstrual blood-derived stem cells (MenSCs). We compared them with and without PRP differentiation medium. MenSCs were then cultured in two experimental groups: with/without PRP differentiation medium and a control group (undifferentiated MenSCs). After 18 days, differentiated cells were analyzed for expression of pancreatic gene markers by real-time PCR. Immunocytochemical staining was used to detect the presence of insulin and Pdx-1 in the differentiated cells, and insulin and C-peptide secretion response to glucose were tested by ELISA. Finally, the morphology of differentiated cells was examined by an inverted microscope. In vitro studies showed that MenSCs differentiated in the PRP differentiation medium had strong properties of IPCs such as pancreatic islet-like structure. The expression of pancreatic markers at both RNA and protein levels showed that the differentiation efficiency was higher in the PRP differentiation medium. In both experimental groups, the differentiated cells were functional and secreted C-peptide and insulin on glucose stimulation, but the secretion of C-peptide and insulin in the PRP group was higher than those cultured in the without PRP differentiation medium. Our findings showed that using of PRP enriched differentiation medium can promote the differentiation of MenSCs into IPCs compared to the without PRP culture group. Therefore, the use of PRP into differentiation media can be proposed as a new approach to producing IPCs from MenSCs and used in cell-based therapies for T1DM.
Asunto(s)
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Plasma Rico en Plaquetas , Humanos , Glucosa/farmacología , Glucosa/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Péptido C/metabolismo , Diferenciación Celular , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células MadreRESUMEN
Ischemia-reperfusion injury refers to a temporary interruption of blood flow in a tissue. Restoration of blood flow initiates the inflammation in tissue causing ischemic damage through the activation of a multiprotein complex termed inflammasome. The complex contains a receptor, mainly a member of nucleotide oligomerization domain-like receptors, that receives danger signals. The receptor is oligomerized as a response to danger signals and then the apoptosis-associated speck-like protein containing a caspase recruitment domain and procaspase protein are added to the oligomerized receptors to form the inflammasome complex. In the next step, the isolated procaspase is converted into an active caspase molecule that initiates the inflammation through the release of interleukin-1ß and interleukin-18. The inflammasome has an important role in the pathogenesis of ischemia-reperfusion injury in different tissues. Here, we summarized the role of inflammasome in the pathogenesis of ischemia-reperfusion of brain, liver, kidney, and heart. Moreover, we highlighted the expression of inflammasome components, the mechanisms involved in activation of the complex, and its inhibition as an optimistic therapeutic technique in ischemia-reperfusion injuries.
Asunto(s)
Inflamasomas , Daño por Reperfusión , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Caspasa 1/metabolismo , Daño por Reperfusión/metabolismo , Inflamación/metabolismoRESUMEN
Gastrointestinal (GI) cancers arise in the GI tract and accessory organs, including the mouth, esophagus, stomach, liver, biliary tract, pancreas, small intestine, large intestine, and rectum. GI cancers are a major cause of cancer-related morbidity and mortality worldwide. Exosomes act as mediators of cell-to-cell communication, with pleiotropic activity in the regulation of homeostasis, and can be markers for diseases. Non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs), can be transported by exosomes derived from tumor cells or non-tumor cells. They can be taken by recipient cells to alter their function or remodel the tumor microenvironment. Moreover, due to their uniquely low immunogenicity and excellent stability, exosomes can be used as natural carriers for therapeutic ncRNAs in vivo. Exosomal lncRNAs have a crucial role in regulating several cancer processes, including angiogenesis, proliferation, drug resistance, metastasis, and immunomodulation. Exosomal lncRNA levels frequently alter according to the onset and progression of cancer. Exosomal lncRNAs can therefore be employed as biomarkers for the diagnosis and prognosis of cancer. Exosomal lncRNAs can also monitor the patient's response to chemotherapy while also serving as potential targets for cancer treatment. Here, we discuss the role of exosomal lncRNAs in the biology and possible future treatment of GI cancer.
RESUMEN
BACKGROUND: The expression pattern of microRNAs in placenta-derived exosomes plays a crucial role in the regulation of immune responses and inflammation at the fetal-maternal interface. OBJECTIVE: Considering the immunomodulatory properties of miR-17 and miR-29a, we determined their expression levels in placenta-derived exosomes in a lipopolysaccharide (LPS)-induced abortion mice model. MATERIALS AND METHODS: A total of 14 pregnant BALB/c mice, aged 6-8 wk, were randomly divided into two groups (n = 7/each) on the gestational day 11.5. While the mice in the experimental group were treated with LPS, those in the control group were treated with Phosphate buffered saline; 5 hr after the treatment, the placental cells were isolated and cultured for 48 hr. Then, the cell culture supernatants were collected and used for isolation of exosomes. The isolated exosomes were confirmed by western blot and scanning electron microscopy. The miRNAs were then extracted from exosomes, and cDNA synthesized. The expression levels of miR-17 and miR-29a were evaluated by quantitative real-time PCR analysis. RESULTS: Our results showed that the expression levels of miR-29a in placenta-derived exosomes obtained from the experimental group increased significantly compared to the control group. Also, the expression levels of miR-17 in the placenta-derived exosomes obtained from the experimental group were found to decrease; however, it did not show significant changes compared with the control group (p > 0.05). CONCLUSION: Inflammatory reactions at the fetal-maternal interface can alter miRNAs expression patterns in placenta-derived exosomes, especially miRNAs with immunomodulatory effects such as miR-29a.
RESUMEN
BACKGROUND: The application of non-viral systems for delivering genes to cells is becoming a very interesting issue, especially in the treatment of neoplasms such as Breast Cancer (BC). Polymer-based non-viral systems are safe and feasible gene carriers to be used in targeted cancer therapy. SALL4 gene encodes a transcription factor and is overexpressed in some cancers. METHODS: In this study, carboxyalkylated-PEI25 (25 kDa) was used to deliver plasmids expressing SALL4-siRNA into MCF-7 cells. DLS and AFM were applied to determine the size of nanoparticles. The MTT method was used to assess cytotoxicity, and the efficiency of transfection was confirmed both qualitatively and quantitatively. Finally, the effect of silencing SALL4 was investigated on the migration of MCF7 cells using the scratch test. RESULTS: The results showed that transferring the SALL4-siRNA using PEI25G10C50 reduced the expression of the corresponding transcription factor by 14 folds which attenuated the migration of MCF-7 cells by 58%. CONCLUSION: In conclusion, PEI25G10C50 can serve as an effective gene delivery system for treating BC by targeting SALL-4.
RESUMEN
Spinal cord injury (SCI) as a crippling disability causes tissue degeneration via neuron loss and fiber disruption. Some researchers have tried to reverse or minimize these changes. Platelet-rich plasma (PRP) is a biological product derived from peripheral blood containing a variety of growth factors. PRP has been extensively used in regenerative medicine. On the other hand, via secreting neuroprotective growth factors, mesenchymal stem cells (MSCs) have shown a promising potential in repairing central nervous system deficits. This study investigated the therapeutic effect of the combined use of MSCs and PRP in a rat model of SCI. We used real time-PCR method for evaluation of Bcl-2, Bax and caspase 3 expressions, TUNEL test for apoptotic cell death assessment, and neurofilament NF200 immunohistochemistry for examination of axonal regeneration. The results showed that co-treatment with MSCs and PRP efficiently alleviated the evaluated categories. Significant differences were observed in expression of Bcl-2 and caspase3, but not Bax, apoptotic index and the number of NF200 positive axons (for all P ≤ 0.01) between co-treatment animals compared with those treated with only MSCs or PRP. In conclusion, this study showed that combination of MSCs and PRP synergistically promotes their therapeutic effects in the SCI.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Traumatismos de la Médula Espinal/terapia , Animales , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Terapia Combinada , Masculino , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
With regard to lifestyle and diet, one of the problems that threaten mankind is diabetes. Given the lack of responsiveness to available drug therapies, the advances made in recent decades in tissue engineering and cell therapy have created a great deal of hope for the treatment of this disease. In this study, silk nanofibrous scaffold (3D) was fabricated by electrospinning and then its biocompatibility and non-toxicity by MTT assay. After that, scaffold supportive effects on human induced pluripotent stem cells (hiPSCs) differentiation to insulin producing cells (IPCs) was studied at the gene and protein levels. IPCs related genes and proteins were up regulated in electrospun silk group significantly greater than tissue culture plates group (2D). In addition, another part of the results demonstrated that differentiated cells on 2D and 3D groups have great functional properties including C-peptide and insulin secreting. It can be concluded that silk nanofibers has a great potential for use in pancreatic tissue engineering applications by support viability, growth and IPCs differentiation of iPSCs.
Asunto(s)
Técnicas de Cultivo de Célula/métodos , Diferenciación Celular/fisiología , Células Madre Pluripotentes Inducidas/citología , Insulina/metabolismo , Nanofibras/química , Seda/química , Técnicas de Cultivo de Célula/instrumentación , Supervivencia Celular , Expresión Génica , Marcadores Genéticos , Transportador de Glucosa de Tipo 2/genética , Proteínas de Homeodominio/genética , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Insulina/genética , Islotes Pancreáticos/fisiología , Andamios del Tejido , Transactivadores/genéticaRESUMEN
Prostate cancer is the most prevalent nonskin cancer and a major cause of cancer-related deaths worldwide. Prostate-specific antigen (PSA) testing is routinely used for screening and early detection of prostate cancer; however, it does not reduce death from prostate cancer. Moreover, PSA is not specific for prostate cancer and results in high false-positive rates, and it is poorly correlated with cancer stage. Therefore, the need for another diagnostic and prognostic factor in prostate cancer is apparent. MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs which are involved in modulation of gene expression posttranscriptionally. Multiple lines of evidence indicate that miRNAs play key roles in various physiological events. Deregulation of miRNAs is related to initiation and development of various diseases such as prostate cancer. It has been shown that various miRNAs (miR-34, miR-21, miR-155, miR-221, miR-222, and let-7) exert their effects by targeting a variety of cellular and molecular pathways (c-Myc, EZH2, c-RSC, BCL2L2, E2F6, ZEB, HMGA251, and CCND2) involved in prostate cancer pathogenesis. Hence, it seems that miRNA expression profiles can be seen as potential candidates for prognosis, diagnosis, and treatment of prostate cancer. Here, we summarize various miRNAs as prognostic, diagnostic, and therapeutic biomarkers for prostate cancer therapy.
Asunto(s)
Biomarcadores de Tumor/sangre , MicroARNs/sangre , Neoplasias de la Próstata/diagnóstico , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/terapia , TranscriptomaRESUMEN
Repairing the lost or damaged mandible is very difficult and time-consuming, so there is a great hope for tissue engineering to accelerate it. At the present study, electrospinning was applied to fabricate polyvinylidene fluoride (PVDF) and PVDF-polyaniline (PANI) composite scaffolds. In addition, extremely low frequency pulsed electromagnetic field (PEMF) was applied for treating the stem cells derived from dental pulp (DPSCs) when cultured on the nanofibrous scaffolds. Osteoinductive property of the fabricated PVDF, PVDF-PANI scaffold at the presence and absence of the PEMF was investigated by evaluating the common osteogenic differentiation markers in seeded-DPSCs on the scaffold. Results demonstrated that cell attachment, protein adsorption and cells viability were increased when PEMF was applied. In addition, ALP activity, calcium content, osteogenic genes and protein evaluations confirmed that PEMF could significantly increase osteoinductivity of the PVDF while composite with PANI. According to the results, the use of polymers with piezoelectricity and conductivity features plus PEMF exposure has a promising potential to improve the current treatment methods in bone and mandibular defects.
Asunto(s)
Compuestos de Anilina/farmacología , Diferenciación Celular , Campos Electromagnéticos , Células Madre Mesenquimatosas/citología , Osteogénesis , Polivinilos/química , Andamios del Tejido/química , Fosfatasa Alcalina/metabolismo , Calcio/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/efectos de la radiación , Pulpa Dental/citología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de la radiación , Osteogénesis/efectos de los fármacos , Osteogénesis/efectos de la radiación , Resistencia a la Tracción , Ingeniería de TejidosRESUMEN
Fibromodulin (FMOD) is known as one of very important extracellular matrix small leucine-rich proteoglycans. This small leucine-rich proteoglycan has critical roles in the extracellular matrix organization and necessary for repairing of tissue in many organs. Given that the major task of FMOD is the modulation of collagen fibrillogenesis. However, recently observed that FMOD plays very important roles in the modulation of a variety of pivotal biological processes including angiogenesis, regulation of TGF-ß activity, and differentiation of human fibroblasts into pluripotent cells, inflammatory mechanisms, apoptosis and metastatic related phenotypes. Besides these roles, FMOD has been considered as a new tumor-related antigen in some malignancies such as lymphoma, leukemia, and leiomyoma. Taken together, these findings proposed that FMOD could be introduced as diagnostic and therapeutic biomarkers in treatment of various cancers. Herein, for first time, we highlighted the various roles of FMOD in the cancerous conditions. Moreover, we summarized the diagnostic and therapeutic applications of FMOD in cancer therapy.
RESUMEN
Breast cancer is the most prevalent cancers worldwide and causes a significant amount of deaths annually. Spalt-like transcription factor 4 is known as a transcription factor, which has an important role in the proliferation of cancerous cells. Small interfering RNA (siRNA) is a short-chain molecule of 20 to 25 nucleotides that protrude on two sides of the 3', two nucleotides. In this study, using a specific sequence of siRNA against the sequence of this gene, its activity is investigated in the cell line of breast cancer. The breast cancer cells (MCF-7) were cultured and then, using a specific anti-sal-like 4 (SALL4) siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and BCL-2 gene were measured using the real-time polymerase chain reaction method. The specific concentration of siRNA IC50 of the SALL4 gene was 40.35 nmole. Gene expression results indicated that the expression of the Bcl-2 gene in the siRNA group was significantly reduced ( P < 0.05). SiRNA can increase the apoptosis of breast cancer cells by reducing the gene expression of SALL4 gene and Bcl-2; it can be used as a novel targeted therapy. This strategy, in addition to increasing the specificity of the drug, also reduces the side effects when compared with conventional chemotherapy.
Asunto(s)
Apoptosis/genética , Neoplasias de la Mama/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Factores de Transcripción/genética , Neoplasias de la Mama/patología , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Células MCF-7 , ARN Interferente Pequeño/genética , TransfecciónRESUMEN
One of the most lethal cancers among women is breast cancer. MicroRNAs (miRNAs) can be of great importance in the early detection of breast cancer. This study aimed to investigate some miRNAs in the serum of patients with breast cancer compared with the control group. Total RNA was extracted from the serum of patients with breast cancer and healthy volunteers. The expression levels of miRNAs and the genes were assessed using real-time reverse transcriptase-polymerase chain reaction with specific primers. Our data showed that miR-25 and miR-133 were downregulated, and miR-17 was upregulated in patients with breast cancer. Upregulation of miR-17 is related to the poor survival time and increased cell proliferation. The reduced expression of miR-133 and miR-25 is significantly associated with clinical stage, metastasis, and survival time of patients with breast cancer. Expressions of miRNAs miR-17, miR-25, and miR-133 are altered in patients with clinical stage, metastasis, poor survival time.
RESUMEN
Metastasis is known to be one of the important factors associated with cancer-related deaths worldwide. Several cellular and molecular targets are involved in the metastasis process. Among these targets, matrix metalloproteinases (MMPs) play central roles in promoting cancer metastasis. MMPs could contribute toward tumor growth, angiogenesis, migration, and invasion via degradation of the extracellular matrix and activation of pre-pro-growth factors. Therefore, identification of various cellular and molecular pathways that affect MMPs could contribute toward a better understanding of the metastatic pathways involved in various tumors. Micro-RNAs are important targets that could affect MMPs. Multiple lines of evidence have indicated that deregulation of various micro-RNAs, including miR-9, Let-7, miR-10b, and miR-15b, affects metastasis of tumor cells via targeting MMPs.
Asunto(s)
Metaloproteinasas de la Matriz Asociadas a la Membrana/metabolismo , Metaloproteinasas de la Matriz Secretadas/metabolismo , MicroARNs/metabolismo , Metástasis de la Neoplasia/fisiopatología , Neoplasias/enzimología , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Matriz Extracelular/enzimología , Humanos , Neoplasias/patologíaRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is associated with impairments of memory, thinking, language, and reasoning. Despite extensive research aiming at the treatment of AD, durable and complete remissions are rare. Hence, new therapeutic approaches are required. Among various therapeutic approaches, stem cells (ie, neural stem cells, mesenchymal stem cells, and embryonic stem cells) and delivery of protective genes such as encoding nerve growth factor, APOE, and glial cell-derived neurotrophic factor have generated promise in AD therapy. Here, we summarized a variety of effective therapeutic approaches (ie, stem cells, and genes) in AD therapy.
Asunto(s)
Enfermedad de Alzheimer/terapia , Terapia Genética/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Apolipoproteínas E/genética , Células Madre Embrionarias/trasplante , Técnicas de Transferencia de Gen , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Humanos , Células Madre Pluripotentes Inducidas/trasplante , Ratones , Factor de Crecimiento Nervioso/genética , Células-Madre Neurales/trasplanteRESUMEN
Antimicrobial peptides (AMPs) have attracted attentions as a novel antimicrobial agent because of their unique activity against microbes. In the present study, we described a new, previously unreported AMP, moronecidin-like peptide, from Hippocampus comes and compared its antimicrobial activity with moronecidin from hybrid striped bass. Antibacterial assay indicated that gram-positive bacteria were more sensitive to moronecidin and moronecidin-like compared with gram-negative bacteria. Furthermore, both AMPs were found to exhibit effective antifungal activity. Comparative analysis of the antimicrobial activity revealed that moronecidin-like peptide has higher activity against Acinetobacter baumannii and Staphylococcus epidermidis relative to moronecidin. Both moronecidin-like and moronecidin peptides retained their antibacterial activity in physiological pH and salt concentration. The time-killing assay showed that the AMPs completely killed A. baumannii and S. epidermidis isolates after 1 and 5 h at five- and tenfold above their corresponding MICs, respectively. Anti-biofilm assay demonstrated that peptides were able to inhibit 50% of biofilm formation at sub-MIC of 1/8 MIC. Furthermore, moronecidin-like significantly inhibited biofilm formation more than moronecidin at 1/16 MIC. Collectively, our results revealed that antimicrobial and anti-biofilm activities of moronecidin-like are comparable to moronecidin. In addition, the hemolytic and cytotoxic activities of moronecidin-like were lower than those of moronecidin, suggesting it as a potential novel therapeutic agent, and a template to design new therapeutic AMPs.
Asunto(s)
Antibacterianos/farmacología , Péptidos/farmacología , Smegmamorpha/metabolismo , Acinetobacter baumannii/efectos de los fármacos , Animales , Antibacterianos/efectos adversos , Péptidos Catiónicos Antimicrobianos/farmacología , Biopelículas/efectos de los fármacos , Proteínas de Peces/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Péptidos/efectos adversos , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
Curcumin is a yellow-orange powder derived from the Curcuma longa plant. Curcumin has been used extensively in traditional medicine for centuries. This component is non-toxic and shown different therapeutic properties such as anti-inflammatory, anti-cancer, antiviral, anti-bacterial, anti-fungal, anti-parasites, and anti-oxidant. Hepatitis B virus (HBV) is a small DNA member of the genus Orthohepadnavirus (Hepadnaviridae family) which is a highly contagious blood-borne viral pathogen. HBV infection is a major public health problem with 2 billion people infected throughout the world and 350 million suffering from chronic HBV infection. Increasing evidence indicated that curcumin as a natural product could be employed in the treatment of HBV patients. It has been showed that curcumin exerts its therapeutic effects on HBV patients via targeting a variety of cellular and molecular pathways such as Wnt/ß-catenin, Ap1, STAT3, MAPK, and NF-κB signaling. Here, we summarized the therapeutic effects of curcumin on patients who infected with HBV. Moreover, we highlighted main signaling pathways (eg, NF-κB, AP1, and Wnt/ß-catenin signaling) which affected by curcumin in HBV infections.
Asunto(s)
Curcumina/uso terapéutico , FN-kappa B/metabolismo , Factor de Transcripción AP-1/metabolismo , beta Catenina/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/patogenicidad , Humanos , Transducción de Señal/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Interferon γ-induced protein 10â¯kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis.
Asunto(s)
Quimiocina CXCL10/metabolismo , Neoplasias Pulmonares/terapia , Melanoma Experimental/terapia , Células Madre Mesenquimatosas/metabolismo , Tejido Adiposo/citología , Adulto , Animales , Línea Celular Tumoral , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células Cultivadas , Quimiocina CXCL10/genética , Modelos Animales de Enfermedad , Terapia Genética/métodos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Masculino , Melanoma Experimental/genética , Melanoma Experimental/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos C57BL , Análisis de Supervivencia , Adulto JovenRESUMEN
One of the important strategies for the treatment of cancer is gene therapy which has the potential to exclusively eradicate malignant cells, without any damage to the normal tissues. Gene-directed enzyme prodrug therapy (GDEPT) is a two-step gene therapy approach, where a suicide gene is directed to tumor cells. The gene encodes an enzyme that expressed intracellularly where it is able to convert a prodrug into cytotoxic metabolites. Various delivery systems have been developed to achieve the appropriate levels of tumor restricted expression of chemotherapeutic drugs. Nowadays, mesenchymal stem cells (MSCs) have been drawing great attention as cellular vehicles for gene delivery systems. Inherent characteristics of MSCs make them particularly attractive gene therapy tools in cell therapy. They have been used largely for their remarkable homing property toward tumor sites and availability from many different adult tissues and show anti-inflammatory actions in some cases. They do not stimulate proliferative responses of lymphocytes, suggests that MSCs have low immunogenicity and could avoid immune rejection. This review summarizes the current state of knowledge about genetically modified MSCs that enable to co-transduce a variety of therapeutic agents including suicide genes (i.e., cytosine deaminase, thymidine kinase) in order to exert potent anti-carcinogenesis against various tumors growth. Moreover, we highlighted the role of exosomes released from MSCs as new therapeutic platform for targeting various therapeutic agents.
Asunto(s)
Marcación de Gen , Terapia Genética , Células Madre Mesenquimatosas/citología , Neoplasias/terapia , Animales , Marcación de Gen/métodos , Técnicas de Transferencia de Gen , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Neoplasias/genéticaRESUMEN
Depression is known as one of important psychiatric disorders which could be associated with disability among various populations. Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV) and international statistical classification of diseases and related health problems (ICD-10) could be used as subjective diagnostic schemes for identification of mental disorders such as depression. Utilization of subjective diagnostic schemes are associated with limitations. Hence, it seems that employing of new diagnosis platforms is required. Multiple lines of evidence indicated that measurement of several biomarkers could be useful for detection patients with depression. Among of various types of biomarkers, microRNAs (miRNAs) have been emerged as powerful tools for diagnosis patients with depression. MiRNAs are small non-coding RNAs which act as epigenetic regulators. It has been showed that these molecules have critical roles in pathogenesis of many diseases such as depression. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in initiation and progression of depression. Hence, miRNAs could be used as diagnostic and therapeutic biomarkers in patients with depression. Besides miRNAs, exosomes as nano- carriers could have been emerged as diagnostic biomarkers in several diseases such as depression. These vesicles are able to carry several cargos such as DNAs, proteins, mRNAs, and miRNAs to recipient cells. Here, we summarized several miRNAs involved in pathogenesis and response to treatment of depression which could be used as diagnostic biomarkers. Moreover, we highlighted exosomes as new diagnostic biomarkers for patients with depression.