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Papers by Morvarid Saeinasab

Journal of translational medicine, May 30, 2024

Biomimetics

The current review aimed to assess the reliability and efficacy of tissue-engineered composite gr... more The current review aimed to assess the reliability and efficacy of tissue-engineered composite grafts in the reconstruction of large maxillofacial defects resulting from trauma or a benign pathologic disease. A systematic review of the literature was conducted using PubMed/Medline, Embase, and Scopus up to March 2022. The eligibility criteria included patients who had been treated with composite allogeneic tissue engineering for immediate/delayed reconstruction of large maxillofacial defects with minimum/no bone harvesting site. In the initial search, 2614 papers were obtained, and finally, 13 papers were eligible to be included in the current study. Most included papers were case reports or case series. A total of 144 cases were enrolled in this systematic review. The mean age of the patients was 43.34 (age range: 9–89). Most studies reported a successful outcome. Bone tissue engineering for the reconstruction and regeneration of crucial-sized maxillofacial defects is an evolving s...

Materials Today Communications

Journal of Functional Biomaterials

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the... more Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodeg...

Applied Sciences

The aim of this review paper is to concentrate on the use and application of photonics in dentist... more The aim of this review paper is to concentrate on the use and application of photonics in dentistry. More than one hundred review and research articles were comprehensively analysed in terms of applications of photonics in dentistry, including surgical applications, as well as dental biomaterials, diagnosis and treatments. In biomedical engineering, various fields, such as biology, chemistry, material and physics, come together in to tackle a disease/disorder either as a diagnostic tool or an option for treatment. Engineers believe that biophotonics is the application of photonics in medicine, whereas photonics is simply a technology for creating and connecting packets of light energy, known as photons. This review paper provides a comprehensive discussion of its main elements, such as photoelasticity, interferometry techniques, optical coherence tomography, different types of lasers, carbon nanotubes, graphene and quantum dots.

Materials, 2021

The current study aimed to evaluate the characteristics and the effects of degradation on the str... more The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored b...

Materials, 2021

Electrospinning is an innovative new fibre technology that aims to design and fabricate membranes... more Electrospinning is an innovative new fibre technology that aims to design and fabricate membranes suitable for a wide range of tissue engineering (TE) applications including vascular grafts, which is the main objective of this research work. This study dealt with fabricating and characterising bilayer structures comprised of an electrospun sheet made of polycaprolactone (PCL, inner layer) and an outer layer made of poly lactic-co-glycolic acid (PLGA) and a coaxial porous scaffold with a micrometre fibre structure was successfully produced. The membranes’ propriety for intended biomedical applications was assessed by evaluating their morphological structure/physical properties and structural integrity when they underwent the degradation process. A scanning electron microscope (SEM) was used to assess changes in the electrospun scaffolds’ structural morphology such as in their fibre diameter, pore size (μm) and the porosity of the scaffold surface which was measured with Image J softw...

Biomimetics, 2021

Liver tissue engineering is a rapidly developing field which combines the novel use of liver cell... more Liver tissue engineering is a rapidly developing field which combines the novel use of liver cells, appropriate biochemical factors, and engineering principles, in order to replace or regenerate damaged liver tissue or the organ. The aim of this review paper is to critically investigate different possible methods to tackle issues related with liver diseases/disorders mainly using regenerative medicine. In this work the various regenerative treatment options are discussed, for improving the prognosis of chronic liver disorders. By reviewing existing literature, it is apparent that the current popular treatment option is liver transplantation, although the breakthroughs of stem cell-based therapy and bioartificial liver technology make them a promising alternative.

Bioengineering, 2021

The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving ... more The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstru...

Biomaterials Science, 2020

Cornea tissue is in high demand by tissue donation centres globally, and thus tissue engineering ... more Cornea tissue is in high demand by tissue donation centres globally, and thus tissue engineering cornea, which is the main topic of corneal translational medicine, can serve as a limitless alternative to a donated human cornea tissue.

International Journal of Biological Macromolecules, Dec 31, 2023

Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound he... more Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound healing in which blastema formation is involved in replacement of injured tissues. It has been suggested that isolated cells from regenerating rabbit ear possess stem-like properties. In this study, we aimed to determine the expression of stemness markers, OCT4 and SOX2 proteins, in regenerating rabbit tissues by immunohistochemistry. Results indicated that both proteins could be detected in epithelial cells, hair follicle cells and perichondrium cells. Expression pattern analysis of OCT4 and SOX2 proteins showed no clear differences between regenerative and non-regenerative control tissues. According to several reports of OCT4 and SOX2 proteins expression in adult stem cells, it could be proposed that OCT4 and SOX2 expressing cells in regenerating rabbit ear tissues are progenitor/adult stem cells which are resident in these tissues, and other markers should be used for detection of blast...

Journal of Experimental & Clinical Cancer Research

In the original publication of this article,[1] the Funding section needs to be revised, and the ... more In the original publication of this article,[1] the Funding section needs to be revised, and the corrected Funding section appears below.

Cellular Reprogramming, 2016

Cell Stemness can be achieved by various reprogramming techniques namely, somatic cell nuclear tr... more Cell Stemness can be achieved by various reprogramming techniques namely, somatic cell nuclear transfer, cell fusion, cell extracts, and introduction of transcription factors from which induced pluripotent stem cells (iPSCs) are obtained. iPSCs are valuable cell sources for drug screening and human disease modeling. Alternatives to virus-based introduction of transcription factors include application of DNA-free methods and introduction of chemically defined culturing conditions. However, the possibility of tumor development is still a hurdle. By taking advantage of NTERA-2 cells, a human embryonal carcinoma cell line, we obtained partially differentiated cells and examined the dedifferentiation capacity of regenerative tissue from rabbit ears. Results indicated that treatment of partially differentiated NTERA-2 cells with the regenerating tissue-conditioned medium (CM) induced expression of key pluripotency markers as examined by real-time polymerase chain reaction, flow cytometry, and immunocytochemistry techniques. In this study, it is reported for the first time that the CM obtained from rabbit regenerating tissue contains dedifferentiation factors, taking cells back to the pluripotency. This system could be a simple and efficient way to reprogram the differentiated cells and generate iPSCs for clinical applications as this system is not accompanied by any viral vector, and reprograms the cells within 10 days of treatment. The results may convince the genomic experts to study the unknown signaling pathways involved in the dedifferentiation by regenerating tissue-CM to authenticate the reprogramming model.

Tumor Biology, 2015

Digestive tract malignancies, including oral, pharyngeal, esophageal, gastric, and colorectal can... more Digestive tract malignancies, including oral, pharyngeal, esophageal, gastric, and colorectal cancers, are among the top 10 most common cancers worldwide. In spite of using various treatment modalities, cancer patients still suffer from recurrence and metastasis of malignant cells. Cancer stem cells (CSCs) are undifferentiated and highly proliferative malignant cells with unique properties mediated by overexpression of stemness markers, metastasis-related proteins, drug transporters, and DNA repair machinery. Due to their salient characteristics, it has been suggested that CSCs are responsible for tumor initiation, progression, invasion, recurrence, and therapy resistance. Exploring different aspects of CSC biology has fueled a great enthusiasm in designing novel therapeutic strategies to help patients. For instance, identification of markers associated with digestive tract CSCs, such as CD44, CD133, CD24, EpCAM, LGR5, ALDH1, and BMI1, has made it possible to develop more accurate diagnosis approaches. In addition, specifically targeting CSCs by their markers imposes fewer side effects and improves therapeutic outcomes. Here, we focus on the current status of CSC biology in digestive tract cancers, with emphasis on CSC markers, and review achieved progress in eradication of digestive tract CSC cells.

ABSTRACT Essential oils, with plant origin, have been of special attention in cancer research dur... more ABSTRACT Essential oils, with plant origin, have been of special attention in cancer research during recent years. Despite many reports on cytotoxic effects of plants from genus salvia, the potential application of their extracts in cancer therapy remains to be assessed in more precise and detailed examinations on the main cause of such effects. In this research, the cytotoxic effect and anticancer activity of essential oils from S. leriifolia on human Transitional Cell Carcinomaa (TCC) were studied in vitro. The antiproliferative activity of essential oils on TCC and L929 (control) cells was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay, by which the mitochondrial dehydrogenase enzyme activity is assessed based on reduction of the MTT to purple. The amount of essential oils to induce 50% of cells to die, designated as IC 50 , was determined by repeated experiments and application of different doses of the essence. The established IC 50 on TCC cells for the essences extracted in two different years of 2006 and 2008 and from two locations of Bajestan and Neyshabour was respectively as: 466 and 250 µg/ml, and 233 and 212 µg/ml. S. leriifolia essential oil did not show any detectable effect on L929 cells in this range of concentration. S. leriifolia essential oil has inhibitory effects on the growth of both TCC and normal L929 cell lines, although the effective concentrations were significantly different in these cell lines. This effect was dose dependent.

Chemotherapy is one of the main strategies for reducing the rate of cancer progression or, in som... more Chemotherapy is one of the main strategies for reducing the rate of cancer progression or, in some cases, curing the tumour. Since a great number of chemotherapeutic agents are cytotoxic compounds, i. e. similarly affect normal and neoplastic cells, application of antitumour drugs is preferred in cancer management and therapy. In this study, the cytotoxicity of diversin was evaluated in 5637 cells, a transitional cell carcinoma (TCC) subline (bladder carcinoma), and normal human fibroblast cells using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Chromatin condensation and DNA damage induced by diversin were also determined by means of 4 ,6-diamidino-2phenylindole (DAPI) staining and the comet assay, respectively. In addition, the mechanism of action of diversin was studied in more detail by the caspase 3 colourimetric assay and flow cytometry-based cell-cycle analyses (PI staining). Our results revealed that diversin has considerable cytotoxic effects in 5637 cells, but not on HFF3 (human foreskin fibroblast) and HDF1 (human dermal fibroblast) cells. Further studies showed that diversin exerts its cytotoxicity via induction of chromatin condensation, DNA damage, and activation of caspase 3 in 5637 cells. In addition, flow cytometric analyses revealed that 5637 cells are mostly arrested at the G2 phase of the cell cycle in the presence of diversin.

Cytotechnology, 2014

Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capaci... more Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capacities. Regeneration is a phenomenon that occurs in a limited number of animals after injury, during which blastema tissue is formed. It has been hypothesized that upon injury, the dedifferentiation of surrounding tissues leads into the appearance of cells with SC characteristics. In present study, stem-like cells (SLCs) were obtained from regenerating tissue of New Zealand white rabbit's pinna and their stemness properties were examined by their capacity to differentiate toward insulin producing cells (IPCs), as well as neural and osteogenic lineages. Differentiation was induced by culture of SLCs in defined medium, and cell fates were monitored by specific staining, RT-PCR and flow cytometry assays. Our results revealed that dithizone positive cells, which represent IPCs, and islet-like structures appeared 1 week after induction of SLCs, and this observation was confirmed by the elevated expression of Ins, Pax6 and Glut4 at mRNA level. Furthermore, SLCs were able to express neural markers as early as 1 week after retinoic acid treatment. Finally, SLCs were able to differentiate into osteogenic lineage, as confirmed by Alizarin Red S staining and RT-PCR studies. In conclusion, SLCs, which could successfully differentiate into cells derived from all three germ layers, can be considered as a valuable model to study developmental biology and regenerative medicine.

Journal of Experimental & Clinical Cancer Research

Background: Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types ... more Background: Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types of cancers, however our understanding of their role in the disease is still very limited. Methods: We applied RNAseq analysis from patient-derived data with validation in independent cohort of patients. We followed these studies with gene regulation analysis as well as experimental dissection of the role of the identified lncRNA by multiple in vitro and in vivo methods. Results: We analyzed RNA-seq data from tumors of 456 CRC patients compared to normal samples, and identified SNHG15 as a potentially oncogenic lncRNA that encodes a snoRNA in one of its introns. The processed SNHG15 is overexpressed in CRC tumors and its expression is highly correlated with poor survival of patients. Interestingly, SNHG15 is more highly expressed in tumors with high levels of MYC expression, while MYC protein binds to two Ebox motifs on SNHG15 sequence, indicating that SNHG15 transcription is directly regulated by the oncogene MYC. The depletion of SNHG15 by siRNA or CRISPR-Cas9 inhibits cell proliferation and invasion, decreases colony formation as well as the tumorigenic capacity of CRC cells, whereas its overexpression leads to opposite effects. Gene expression analysis performed upon SNHG15 inhibition showed changes in multiple relevant genes implicated in cancer progression, including MYC, NRAS, BAG3 or ERBB3. Several of these genes are functionally related to AIF, a protein that we found to specifically interact with SNHG15, suggesting that the SNHG15 acts, at least in part, by regulating the activity of AIF. Interestingly, ROS levels, which are directly regulated by AIF, show a significant reduction in SNHG15-depleted cells. Moreover, knockdown of SNHG15 increases the sensitiveness of the cells to 5-FU, while its overexpression renders them more resistant to the chemotherapeutic drug. Conclusion: Altogether, these results describe an important role of SNHG15 in promoting colon cancer and mediating drug resistance, suggesting its potential as prognostic marker and target for RNA-based therapies.

Journal of translational medicine, May 30, 2024

Biomimetics

The current review aimed to assess the reliability and efficacy of tissue-engineered composite gr... more The current review aimed to assess the reliability and efficacy of tissue-engineered composite grafts in the reconstruction of large maxillofacial defects resulting from trauma or a benign pathologic disease. A systematic review of the literature was conducted using PubMed/Medline, Embase, and Scopus up to March 2022. The eligibility criteria included patients who had been treated with composite allogeneic tissue engineering for immediate/delayed reconstruction of large maxillofacial defects with minimum/no bone harvesting site. In the initial search, 2614 papers were obtained, and finally, 13 papers were eligible to be included in the current study. Most included papers were case reports or case series. A total of 144 cases were enrolled in this systematic review. The mean age of the patients was 43.34 (age range: 9–89). Most studies reported a successful outcome. Bone tissue engineering for the reconstruction and regeneration of crucial-sized maxillofacial defects is an evolving s...

Materials Today Communications

Journal of Functional Biomaterials

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the... more Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodeg...

Applied Sciences

The aim of this review paper is to concentrate on the use and application of photonics in dentist... more The aim of this review paper is to concentrate on the use and application of photonics in dentistry. More than one hundred review and research articles were comprehensively analysed in terms of applications of photonics in dentistry, including surgical applications, as well as dental biomaterials, diagnosis and treatments. In biomedical engineering, various fields, such as biology, chemistry, material and physics, come together in to tackle a disease/disorder either as a diagnostic tool or an option for treatment. Engineers believe that biophotonics is the application of photonics in medicine, whereas photonics is simply a technology for creating and connecting packets of light energy, known as photons. This review paper provides a comprehensive discussion of its main elements, such as photoelasticity, interferometry techniques, optical coherence tomography, different types of lasers, carbon nanotubes, graphene and quantum dots.

Materials, 2021

The current study aimed to evaluate the characteristics and the effects of degradation on the str... more The current study aimed to evaluate the characteristics and the effects of degradation on the structural properties of Poly(lactic-co-glycolic acid) (PLGA)- and polycaprolactone (PCL)-based nanofibrous scaffolds. Six scaffolds were prepared by electrospinning, three with PCL 15% (w/v) and three with PLGA 10% (w/v), with electrospinning processing times of 30, 60 and 90 min. Both types of scaffolds displayed more robust mechanical properties with increased spinning times. The tensile strength of both scaffolds with 90-min electrospun membranes did not show a significant difference in their strengths, as the PCL and PLGA scaffolds measured at 1.492 MPa ± 0.378 SD and 1.764 MPa ± 0.7982 SD, respectively. All membranes were shown to be hydrophobic under a wettability test. A degradation behaviour study was performed by immersing all scaffolds in phosphate-buffered saline (PBS) solution at room temperature for 12 weeks and for 4 weeks at 37 °C. The effects of degradation were monitored b...

Materials, 2021

Electrospinning is an innovative new fibre technology that aims to design and fabricate membranes... more Electrospinning is an innovative new fibre technology that aims to design and fabricate membranes suitable for a wide range of tissue engineering (TE) applications including vascular grafts, which is the main objective of this research work. This study dealt with fabricating and characterising bilayer structures comprised of an electrospun sheet made of polycaprolactone (PCL, inner layer) and an outer layer made of poly lactic-co-glycolic acid (PLGA) and a coaxial porous scaffold with a micrometre fibre structure was successfully produced. The membranes’ propriety for intended biomedical applications was assessed by evaluating their morphological structure/physical properties and structural integrity when they underwent the degradation process. A scanning electron microscope (SEM) was used to assess changes in the electrospun scaffolds’ structural morphology such as in their fibre diameter, pore size (μm) and the porosity of the scaffold surface which was measured with Image J softw...

Biomimetics, 2021

Liver tissue engineering is a rapidly developing field which combines the novel use of liver cell... more Liver tissue engineering is a rapidly developing field which combines the novel use of liver cells, appropriate biochemical factors, and engineering principles, in order to replace or regenerate damaged liver tissue or the organ. The aim of this review paper is to critically investigate different possible methods to tackle issues related with liver diseases/disorders mainly using regenerative medicine. In this work the various regenerative treatment options are discussed, for improving the prognosis of chronic liver disorders. By reviewing existing literature, it is apparent that the current popular treatment option is liver transplantation, although the breakthroughs of stem cell-based therapy and bioartificial liver technology make them a promising alternative.

Bioengineering, 2021

The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving ... more The cornea comprises a pool of self-regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self-renewing and skeletal tissues, hold immense interest for tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstru...

Biomaterials Science, 2020

Cornea tissue is in high demand by tissue donation centres globally, and thus tissue engineering ... more Cornea tissue is in high demand by tissue donation centres globally, and thus tissue engineering cornea, which is the main topic of corneal translational medicine, can serve as a limitless alternative to a donated human cornea tissue.

International Journal of Biological Macromolecules, Dec 31, 2023

Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound he... more Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound healing in which blastema formation is involved in replacement of injured tissues. It has been suggested that isolated cells from regenerating rabbit ear possess stem-like properties. In this study, we aimed to determine the expression of stemness markers, OCT4 and SOX2 proteins, in regenerating rabbit tissues by immunohistochemistry. Results indicated that both proteins could be detected in epithelial cells, hair follicle cells and perichondrium cells. Expression pattern analysis of OCT4 and SOX2 proteins showed no clear differences between regenerative and non-regenerative control tissues. According to several reports of OCT4 and SOX2 proteins expression in adult stem cells, it could be proposed that OCT4 and SOX2 expressing cells in regenerating rabbit ear tissues are progenitor/adult stem cells which are resident in these tissues, and other markers should be used for detection of blast...

Journal of Experimental & Clinical Cancer Research

In the original publication of this article,[1] the Funding section needs to be revised, and the ... more In the original publication of this article,[1] the Funding section needs to be revised, and the corrected Funding section appears below.

Cellular Reprogramming, 2016

Cell Stemness can be achieved by various reprogramming techniques namely, somatic cell nuclear tr... more Cell Stemness can be achieved by various reprogramming techniques namely, somatic cell nuclear transfer, cell fusion, cell extracts, and introduction of transcription factors from which induced pluripotent stem cells (iPSCs) are obtained. iPSCs are valuable cell sources for drug screening and human disease modeling. Alternatives to virus-based introduction of transcription factors include application of DNA-free methods and introduction of chemically defined culturing conditions. However, the possibility of tumor development is still a hurdle. By taking advantage of NTERA-2 cells, a human embryonal carcinoma cell line, we obtained partially differentiated cells and examined the dedifferentiation capacity of regenerative tissue from rabbit ears. Results indicated that treatment of partially differentiated NTERA-2 cells with the regenerating tissue-conditioned medium (CM) induced expression of key pluripotency markers as examined by real-time polymerase chain reaction, flow cytometry, and immunocytochemistry techniques. In this study, it is reported for the first time that the CM obtained from rabbit regenerating tissue contains dedifferentiation factors, taking cells back to the pluripotency. This system could be a simple and efficient way to reprogram the differentiated cells and generate iPSCs for clinical applications as this system is not accompanied by any viral vector, and reprograms the cells within 10 days of treatment. The results may convince the genomic experts to study the unknown signaling pathways involved in the dedifferentiation by regenerating tissue-CM to authenticate the reprogramming model.

Tumor Biology, 2015

Digestive tract malignancies, including oral, pharyngeal, esophageal, gastric, and colorectal can... more Digestive tract malignancies, including oral, pharyngeal, esophageal, gastric, and colorectal cancers, are among the top 10 most common cancers worldwide. In spite of using various treatment modalities, cancer patients still suffer from recurrence and metastasis of malignant cells. Cancer stem cells (CSCs) are undifferentiated and highly proliferative malignant cells with unique properties mediated by overexpression of stemness markers, metastasis-related proteins, drug transporters, and DNA repair machinery. Due to their salient characteristics, it has been suggested that CSCs are responsible for tumor initiation, progression, invasion, recurrence, and therapy resistance. Exploring different aspects of CSC biology has fueled a great enthusiasm in designing novel therapeutic strategies to help patients. For instance, identification of markers associated with digestive tract CSCs, such as CD44, CD133, CD24, EpCAM, LGR5, ALDH1, and BMI1, has made it possible to develop more accurate diagnosis approaches. In addition, specifically targeting CSCs by their markers imposes fewer side effects and improves therapeutic outcomes. Here, we focus on the current status of CSC biology in digestive tract cancers, with emphasis on CSC markers, and review achieved progress in eradication of digestive tract CSC cells.

ABSTRACT Essential oils, with plant origin, have been of special attention in cancer research dur... more ABSTRACT Essential oils, with plant origin, have been of special attention in cancer research during recent years. Despite many reports on cytotoxic effects of plants from genus salvia, the potential application of their extracts in cancer therapy remains to be assessed in more precise and detailed examinations on the main cause of such effects. In this research, the cytotoxic effect and anticancer activity of essential oils from S. leriifolia on human Transitional Cell Carcinomaa (TCC) were studied in vitro. The antiproliferative activity of essential oils on TCC and L929 (control) cells was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay, by which the mitochondrial dehydrogenase enzyme activity is assessed based on reduction of the MTT to purple. The amount of essential oils to induce 50% of cells to die, designated as IC 50 , was determined by repeated experiments and application of different doses of the essence. The established IC 50 on TCC cells for the essences extracted in two different years of 2006 and 2008 and from two locations of Bajestan and Neyshabour was respectively as: 466 and 250 µg/ml, and 233 and 212 µg/ml. S. leriifolia essential oil did not show any detectable effect on L929 cells in this range of concentration. S. leriifolia essential oil has inhibitory effects on the growth of both TCC and normal L929 cell lines, although the effective concentrations were significantly different in these cell lines. This effect was dose dependent.

Chemotherapy is one of the main strategies for reducing the rate of cancer progression or, in som... more Chemotherapy is one of the main strategies for reducing the rate of cancer progression or, in some cases, curing the tumour. Since a great number of chemotherapeutic agents are cytotoxic compounds, i. e. similarly affect normal and neoplastic cells, application of antitumour drugs is preferred in cancer management and therapy. In this study, the cytotoxicity of diversin was evaluated in 5637 cells, a transitional cell carcinoma (TCC) subline (bladder carcinoma), and normal human fibroblast cells using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Chromatin condensation and DNA damage induced by diversin were also determined by means of 4 ,6-diamidino-2phenylindole (DAPI) staining and the comet assay, respectively. In addition, the mechanism of action of diversin was studied in more detail by the caspase 3 colourimetric assay and flow cytometry-based cell-cycle analyses (PI staining). Our results revealed that diversin has considerable cytotoxic effects in 5637 cells, but not on HFF3 (human foreskin fibroblast) and HDF1 (human dermal fibroblast) cells. Further studies showed that diversin exerts its cytotoxicity via induction of chromatin condensation, DNA damage, and activation of caspase 3 in 5637 cells. In addition, flow cytometric analyses revealed that 5637 cells are mostly arrested at the G2 phase of the cell cycle in the presence of diversin.

Cytotechnology, 2014

Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capaci... more Stem cells (SCs) are known as undifferentiated cells with self-renewal and differentiation capacities. Regeneration is a phenomenon that occurs in a limited number of animals after injury, during which blastema tissue is formed. It has been hypothesized that upon injury, the dedifferentiation of surrounding tissues leads into the appearance of cells with SC characteristics. In present study, stem-like cells (SLCs) were obtained from regenerating tissue of New Zealand white rabbit's pinna and their stemness properties were examined by their capacity to differentiate toward insulin producing cells (IPCs), as well as neural and osteogenic lineages. Differentiation was induced by culture of SLCs in defined medium, and cell fates were monitored by specific staining, RT-PCR and flow cytometry assays. Our results revealed that dithizone positive cells, which represent IPCs, and islet-like structures appeared 1 week after induction of SLCs, and this observation was confirmed by the elevated expression of Ins, Pax6 and Glut4 at mRNA level. Furthermore, SLCs were able to express neural markers as early as 1 week after retinoic acid treatment. Finally, SLCs were able to differentiate into osteogenic lineage, as confirmed by Alizarin Red S staining and RT-PCR studies. In conclusion, SLCs, which could successfully differentiate into cells derived from all three germ layers, can be considered as a valuable model to study developmental biology and regenerative medicine.

Journal of Experimental & Clinical Cancer Research

Background: Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types ... more Background: Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types of cancers, however our understanding of their role in the disease is still very limited. Methods: We applied RNAseq analysis from patient-derived data with validation in independent cohort of patients. We followed these studies with gene regulation analysis as well as experimental dissection of the role of the identified lncRNA by multiple in vitro and in vivo methods. Results: We analyzed RNA-seq data from tumors of 456 CRC patients compared to normal samples, and identified SNHG15 as a potentially oncogenic lncRNA that encodes a snoRNA in one of its introns. The processed SNHG15 is overexpressed in CRC tumors and its expression is highly correlated with poor survival of patients. Interestingly, SNHG15 is more highly expressed in tumors with high levels of MYC expression, while MYC protein binds to two Ebox motifs on SNHG15 sequence, indicating that SNHG15 transcription is directly regulated by the oncogene MYC. The depletion of SNHG15 by siRNA or CRISPR-Cas9 inhibits cell proliferation and invasion, decreases colony formation as well as the tumorigenic capacity of CRC cells, whereas its overexpression leads to opposite effects. Gene expression analysis performed upon SNHG15 inhibition showed changes in multiple relevant genes implicated in cancer progression, including MYC, NRAS, BAG3 or ERBB3. Several of these genes are functionally related to AIF, a protein that we found to specifically interact with SNHG15, suggesting that the SNHG15 acts, at least in part, by regulating the activity of AIF. Interestingly, ROS levels, which are directly regulated by AIF, show a significant reduction in SNHG15-depleted cells. Moreover, knockdown of SNHG15 increases the sensitiveness of the cells to 5-FU, while its overexpression renders them more resistant to the chemotherapeutic drug. Conclusion: Altogether, these results describe an important role of SNHG15 in promoting colon cancer and mediating drug resistance, suggesting its potential as prognostic marker and target for RNA-based therapies.