Hojjat Naderi-Meshkin | Queen's University Belfast (original) (raw)

Papers by Hojjat Naderi-Meshkin

Research paper thumbnail of Cardiomyogenic differentiation of human adipose-derived mesenchymal stem cells transduced with Tbx20-encoding lentiviral vectors

Journal of cellular biochemistry, Jan 10, 2018

Ischemic heart disease often results in myocardial infarction and is the leading cause of mortali... more Ischemic heart disease often results in myocardial infarction and is the leading cause of mortality and morbidity worldwide. Improvement in the function of infarcted myocardium is a main purpose of cardiac regenerative medicine. One possible way to reach this goal is via stem cell therapy. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types but display limited cardiomyogenic differentiation potential. Members of the T-box family of transcription factors including Tbx20 play important roles in heart development and cardiomyocyte homeostasis. Therefore, in the current study, we investigated the potential of Tbx20 to enhance the cardiomyogenic differentiation of human adipose-derived MSCs (ADMSCs). Human ADMSCs were transduced with a bicistronic lentiviral vector encoding Tbx20 (murine) and the enhanced green fluorescent protein (eGFP) and analyzed 7 and 14 days post transduction. Transduction of human ADMSCs with this lentivi...

Research paper thumbnail of Use of Stromal Amniotic Membrane as a Suitable Scaffold for Tissue Engineering

Research paper thumbnail of Adipose tissue‐derived mesenchymal stem cells and keratinocytes co‐culture on gelatin/chitosan/β‐glycerol phosphate nanoscaffold in skin regeneration

Cell Biology International, 2019

Using cell‐based engineered skin is an emerging strategy for treating difficult‐to‐heal wounds. T... more Using cell‐based engineered skin is an emerging strategy for treating difficult‐to‐heal wounds. To date, much endeavor has been devoted to the fabrication of appropriate scaffolds with suitable biomechanical properties to support cell viability and growth in the microenvironment of a wound. The aim of this research was to assess the impact of adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) and keratinocytes on gelatin/chitosan/β‐glycerol phosphate (GCGP) nanoscaffold in full‐thickness excisional skin wound healing of rats. For this purpose, AD‐MSCs and keratinocytes were isolated from rats and GCGP nanoscaffolds were electrospun. Through an in vivo study, the percentage of wound closure was assessed on days 7, 14, and 21 after wound induction. Samples were taken from the wound sites in order to evaluate the density of collagen fibers and vessels at 7 and 14 days. Moreover, sampling was done on days 7 and 14 from wound sites to assess the density of collagen fibers and vessel...

Research paper thumbnail of CXCR4: A Potential Chemokine Receptor for Future Regenerative Therapeutic Target

Journal of Cell and Molecular Research, 2015

Understanding the molecular mechanisms in regeneration could help the stem cell therapists to imp... more Understanding the molecular mechanisms in regeneration could help the stem cell therapists to improve the clinical practices and could be considered a major milestone in the translation of stem cell research to clinics. Chemokines have been described as one of the most significant singling networks in stem cells homing and regeneration of damaged organs. CXCR4/CXCL12 has been known as a key player in this regard. Expression of CXCR4 has been observed in a number of cells such as mesenchymal stem cells, epithelial cells etc and plays crucial and unique role in the migration of cells towards a cytokine gradient and regulating stem cells trafficking as well as tissue/organ regeneration and embryogenesis.

Research paper thumbnail of Markers of Pluripotency Can be Induced in Human Keratinocytes after Co-culturing with a Pluripotent Tissue

Research paper thumbnail of A New Approach for Optimization of Keratinocyte Culture and Fabrication of Keratinocyte Epidermal Sheets without Using 3T3 Feeder Layer

Research paper thumbnail of Induction of tenogenic differentiation of equine adipose-derived mesenchymal stem cells by platelet-derived growth factor-BB and growth differentiation factor-6

Molecular biology reports, 2020

Managing tendon healing process is complicated mainly due to the limited regeneration capacity of... more Managing tendon healing process is complicated mainly due to the limited regeneration capacity of tendon tissue. Mesenchymal stem cells (MSCs) have potential applications in regenerative medicine and have been considered for tendon repair and regeneration. This study aimed to evaluate the capacity of equine adipose tissue-derived cells (eASCs) to differentiate into tenocytes in response to platelet-derived growth factor-BB (PDGF-BB) and growth differentiation factor-6 (GDF-6) in vitro. Frozen characterized eASCS of 3 mares were thawed and the cells were expanded in basic culture medium (DMEM supplemented with 10% FBS). The cells at passage 5 were treated for 14 days in different conditions including: (1) control group in basic culture medium (CM), (2) induction medium as IM (CM containing L-prolin, and ascorbic acid (AA)) supplemented with PDGF-BB (20 ng/ml), (3) IM supplemented with GDF-6 (20 ng/ml), and (4) IM supplemented with PDGF-BB and GDF-6. At the end of culture period (14th...

Research paper thumbnail of Differentiation of human adipose-derived mesenchymal stem cells toward tenocyte by platelet-derived growth factor-BB and growth differentiation factor-6

Cell and Tissue Banking

Mesenchymal Stem Cells (MSCs) are important in regenerative medicine and tissue engineering and w... more Mesenchymal Stem Cells (MSCs) are important in regenerative medicine and tissue engineering and will be a very sensible choice for repair and regeneration of tendon. New biological practices, such as cellular therapy using stem cells, are promising for facilitating or expediting tendon therapy. Before using these cells clinically, it is best to check and confirm the optimal conditions for differentiation of these cells in the laboratory. Hence, in the present study, the impacts of PDGF-BB and GDF-6 supplementation on adipose-derived MSCs (ASCs) culture were studied. The frozen ASC were recovered and expanded in basic culture medium (DMEM with 10%FBS). The cells after passage five (P5) were treated with basic medium containing L-Prolin, Ascorbic Acid and only PDGF-BB or GDF-6 (20 ng/ml) or both of them (mix) as 3 groups for 14 days to investigate efficiency of ASCs differentiation towards tenocytes. The cells culturing in basic medium were used as control group. To validate tenogenic differentiation, H&E and Sirius Red staining were used to assess cell morphology and collagen production, respectively. In addition, mRNA levels of collagen I and III, Scleraxis and Tenomodulin as tenogenic markers were analyzed using qPCR. In all test groups, cells appeared slenderer, elongated cytoplasmic attributes compared to the control cells. The intensity of Sirius Red staining was significantly higher in GDF-6, PDGF-BB alone, than in group without supplements. The optical density was higher in the GDF-6 than PDGF-BB and mix-group. QPCR results showed that Col I and III gene expression was increased in all groups compared to the control. SCX expression was significantly increased only in the PDGF-BB group. TNMD mRNA expression was not significant among groups. In this study, we have corroborated that human ASCs are reactionary to tenogenic induction by GDF-6 and PDGF-BB alone or in combination. These outcomes will help greater insight into GDF-6 and PDGF-BB driven tenogenesis of ASCs and new directions of discovery in the design of ASC-based treatments for tendon healing.

Research paper thumbnail of Endothelial Cells Derived From Patients With Diabetic Macular Edema Recapitulate Clinical Evaluations of Anti-VEGF Responsiveness Through the Neuronal Pentraxin 2 Pathway

Research paper thumbnail of CRISPR/Cas9 mediated GFP‐human dentin matrix protein 1 (DMP1) promoter knock‐in at the ROSA26 locus in mesenchymal stem cell for monitoring osteoblast differentiation

The Journal of Gene Medicine

Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone, playing a criti... more Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone, playing a critical role in mineralization and phosphate metabolism. One important role for the expression of DMP1 in the nucleus of preosteoblasts is the up‐regulation of osteoblast‐specific genes such as osteocalcin and alkaline phosphatase1. The present study aimed to investigate the potential application of human DMP1 promoter as an indicator marker of osteoblastic differentiation.

Research paper thumbnail of The effect of adrenocorticotropic hormone on alpha‐2‐macroglobulin in osteoblasts derived from human mesenchymal stem cells

Journal of Cellular and Molecular Medicine

Research paper thumbnail of T-Box20 inhibits osteogenic differentiation in adipose-derived human mesenchymal stem cells: the role of T-Box20 on osteogenesis

Journal of Biological Research-Thessaloniki

Background Skeletal development and its cellular function are regulated by various transcription ... more Background Skeletal development and its cellular function are regulated by various transcription factors. The T-box (Tbx) family of transcription factors have critical roles in cellular differentiation as well as heart and limbs organogenesis. These factors possess activator and/or repressor domains to modify the expression of target genes. Despite the obvious effects of Tbx20 on heart development, its impact on bone development is still unknown. Methods To investigate the consequence by forced Tbx20 expression in the osteogenic differentiation of human mesenchymal stem cells derived from adipose tissue (Ad-MSCs), these cells were transduced with a bicistronic lentiviral vector encoding Tbx20 and an enhanced green fluorescent protein. Results Tbx20 gene delivery system suppressed the osteogenic differentiation of Ad-MSCs, as indicated by reduction in alkaline phosphatase activity and Alizarin Red S staining. Consistently, reverse transcription-polymerase chain reaction analyses show...

Research paper thumbnail of Overexpression of MicroRNA-148b-3p stimulates osteogenesis of human bone marrow-derived mesenchymal stem cells: the role of MicroRNA-148b-3p in osteogenesis

Research paper thumbnail of Regeneration and Repair of Skin Wounds: Various Strategies for Treatment

The International Journal of Lower Extremity Wounds

Skin as a mechanical barrier between the inner and outer environment of our body protects us agai... more Skin as a mechanical barrier between the inner and outer environment of our body protects us against infection and electrolyte loss. This organ consists of 3 layers: the epidermis, dermis, and hypodermis. Any disruption in the integrity of skin leads to the formation of wounds, which are divided into 2 main categories: acute wounds and chronic wounds. Generally, acute wounds heal relatively faster. In contrast to acute wounds, closure of chronic wounds is delayed by 3 months after the initial insult. Treatment of chronic wounds has been one of the most challenging issues in the field of regenerative medicine, promoting scientists to develop various therapeutic strategies for a fast, qualified, and most cost-effective treatment modality. Here, we reviewed more recent approaches, including the development of stem cell therapy, tissue-engineered skin substitutes, and skin equivalents, for the healing of complex wounds.

Research paper thumbnail of Adipocyte lineage differentiation potential of MSCs isolated from reaming material

Journal of Cellular Physiology

Mesenchymal stem cells (MSCs) obtained from various sources have been used for different therapeu... more Mesenchymal stem cells (MSCs) obtained from various sources have been used for different therapeutic applications including tissue regeneration. Reamer/irrigator/aspirator (RIA) has been increasingly used in recent years for the derivation of MSCs. Here in this investigation we have comparatively analyzed MSCs obtained from iliac crest bone marrow (ICBM) and RIA for their morphology, cluster determinant (CD) markers, and adipogenic differentiation capacity. MSCs were isolated, cultured, and purified from both sources and then flow cytometric studies were performed to study their characteristics. The differentiation potential of RIA and ICBM was examined by an Oil Red O staining protocol. Moreover, the tissue‐specific markers related to adipogenesis were analyzed by real‐time polymerase chain reaction (RT‐PCR). The cells were cultured in the relevant induction medium and then adipogenic lineage differentiation was tested and confirmed for all MSC preparations. Additionally, analysis by flow cytometer was indicative of RIA derived MSCs (RIA‐MSCs) having a more homogenous population than ICBM derived MSCs. The RIA‐MSCs differentiation toward adipogenic lineage was more efficient compared with ICBM‐MSCs. Direct comparative analysis of RIA to ICBM‐MSCs indicated that the RIA‐MSCs had a higher potential toward adipocyte lineage differentiation compared with ICBM‐MSCs.

Research paper thumbnail of Cancer metastasis versus stem cell homing: Role of platelets

Journal of Cellular Physiology

One of the major obstacles in achieving a successful stem cell therapy is insufficient homing of ... more One of the major obstacles in achieving a successful stem cell therapy is insufficient homing of transplanted cells. To overcome this obstacle, understanding the underlying mechanisms of stem cell homing is of obvious importance. Central to this review is the concept that cancer metastasis can be viewed as a role model to build up a comprehensive concept of stem cell homing. In this novel perspective, the prosurvival choices of the cancerous cells in the bloodstream, their arrest, extravasation, and proliferation at the secondary site can be exploited in favor of targeted stem cell homing. To date, tumor cells have been found to employ a wide variety of strategies to promote metastasis. One of these strategies is through their ability to activate platelets and subsequently activated platelets serve cancer cell survival and metastasis. Accordingly, in the first part of this review the roles of platelets in cancer metastasis as well as stem cell homing are discussed. Next, we provide some lessons learned from cancer metastasis in favor of developing strategies for improvement of stem cell homing with emphasis on the role of platelets. Based on direct or indirect evidence from metastasis, strategies such as manipulation of stem cells to enhance interaction with platelets, preconditioning–pretreatment of stem cells with platelets in vitro, and coinjection of both stem cells and platelets are proposed to improve stem cell homing.

Research paper thumbnail of Using paracrine effects of Ad-MSCs on keratinocyte cultivation and fabrication of epidermal sheets for improving clinical applications

Cell and Tissue Banking

Recent advances in wound healing have made cell therapy a potential approach for the treatment of... more Recent advances in wound healing have made cell therapy a potential approach for the treatment of various types of skin defects such as trauma, burns, scars and diabetic leg ulcers. Cultured keratinocytes have been applied to burn patients since 1981. Patients with acute and chronic wounds can be treated with autologous/allograft cultured keratinocytes. There are various methods for cultivation of epidermal keratinocytes used in cell therapy. One of the important properties of an efficient cell therapy is the preservation of epidermal stem cells. Mesenchymal Stem Cells (MSCs) are major regulatory cells involved in the acceleration of wound healing via induction of cell proliferation, angiogenesis and stimulating the release of paracrine signaling molecules. Considering the beneficial effects of MSCs on wound healing, the main aim of the present study is investigating paracrine effects of Adipose-derived Mesenchymal Stem Cell (Ad-MSCs) on cultivation of keratinocytes with focusing on preservation of stem cells and their differentiation process. We further introduced a new approach for culturing isolated keratinocytes in vitro in order to generate epidermal keratinocyte sheets without using a feeder layer. To do so, Ad-MSC conditioned medium was applied as an alternative to commercial media for keratinocyte cultivation. In this study, the expression of several stem/progenitor cell (P63, K19 and K14) and differentition (K10, IVL and FLG) markers was examined using real time PCR on days 7, 14 and 21 of culture in keratinocytes in Ad-MSC conditioned medium. P63 and α6 integrin expression was also evaluated via flow cytometry. The results were compared with control group including keratinocytes cultured in EpiLife medium and our data indicated that this Ad-MSC conditioned medium is a good alternative for keratinocyte cultivation and producing epidermal sheets for therapeutic and clinical purposes. The reasons are the expression of stem cell and differentiation markers and overcoming the requirement for feeder layer which leads to a xenograft-free transplantation. Besides, this approach has low cost and is easier to perform. However, more in vitro and in vivo experiments as well as safety evaluation required before clinical applications.

Research paper thumbnail of Effect of bioactive glass nanoparticles on biological properties of PLGA/collagen scaffold

Progress in biomaterials, Jan 11, 2018

Bioactive glasses have shown some interesting biological properties such as biocompatibility, bio... more Bioactive glasses have shown some interesting biological properties such as biocompatibility, biodegradation, and angiogenesis in skin tissue engineering. In the current research, the effects of MgO- or CoO-doped 64S bioactive glass with a composition of 64 SiO-26 CaO-5 PO-5 MgO or CoO (mol%) were studied in relation with biological properties of electrospun [poly(lactic-co-glycolic acid) (PLGA)/collagen]. PLGA/collagen samples were rinsed in suspension of bioactive glass nanoparticles in distilled water with a concentration of 0.1 w/v and then freeze dried. Cell adhesion, viability, angiogenesis, and ionic release were performed and tested in culture medium containing fibroblast cells. Attachment and viability of fibroblast cells were increased significantly in bioglass-coated samples, while shrinkage in PLGA/collagen scaffold was reduced by the addition of bioactive glass. Vascular endothelial growth factor secretion in coated scaffold was dropped compared to the uncoated samples....

Research paper thumbnail of Chemically primed bone-marrow derived mesenchymal stem cells show enhanced expression of chemokine receptors contributed to their migration capability

Iranian journal of basic medical sciences, 2016

The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key ob... more The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key obstacle in MSC-based therapy. It is believed that chemokines and chemokine receptor interactions play key roles in cellular processes associated with migration. Meanwhile, MSCs express a low level of distinct chemokine receptors and they even lose these receptors on their surface after a few passages which influence their therapeutic applications negatively. This study investigated whether treatment of BM-MSCs with hypoxia-mimicking agents would increase expression of some chemokine receptors and cell migration. BM-MSCs were treated at passage 2 for our gene expression profiling. All qPCR experiments were performed by SYBR Green method in CFX-96 Bio-Rad Real-Time PCR. The Boyden chamber assay was utilized to investigate BM-MSC homing. Possible approaches to increasing the expression level of chemokine receptors by different hypoxia-mimicking agents such as valproic acid (VPA), CoCl2, and ...

Research paper thumbnail of Genetically Modified Human Adipose-Derived Mesenchymal Stem Cells Overexpressing CXCR4R334X, a Hyper Functional Mutant Receptor, Display Enhanced Migration

Research paper thumbnail of Cardiomyogenic differentiation of human adipose-derived mesenchymal stem cells transduced with Tbx20-encoding lentiviral vectors

Journal of cellular biochemistry, Jan 10, 2018

Ischemic heart disease often results in myocardial infarction and is the leading cause of mortali... more Ischemic heart disease often results in myocardial infarction and is the leading cause of mortality and morbidity worldwide. Improvement in the function of infarcted myocardium is a main purpose of cardiac regenerative medicine. One possible way to reach this goal is via stem cell therapy. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types but display limited cardiomyogenic differentiation potential. Members of the T-box family of transcription factors including Tbx20 play important roles in heart development and cardiomyocyte homeostasis. Therefore, in the current study, we investigated the potential of Tbx20 to enhance the cardiomyogenic differentiation of human adipose-derived MSCs (ADMSCs). Human ADMSCs were transduced with a bicistronic lentiviral vector encoding Tbx20 (murine) and the enhanced green fluorescent protein (eGFP) and analyzed 7 and 14 days post transduction. Transduction of human ADMSCs with this lentivi...

Research paper thumbnail of Use of Stromal Amniotic Membrane as a Suitable Scaffold for Tissue Engineering

Research paper thumbnail of Adipose tissue‐derived mesenchymal stem cells and keratinocytes co‐culture on gelatin/chitosan/β‐glycerol phosphate nanoscaffold in skin regeneration

Cell Biology International, 2019

Using cell‐based engineered skin is an emerging strategy for treating difficult‐to‐heal wounds. T... more Using cell‐based engineered skin is an emerging strategy for treating difficult‐to‐heal wounds. To date, much endeavor has been devoted to the fabrication of appropriate scaffolds with suitable biomechanical properties to support cell viability and growth in the microenvironment of a wound. The aim of this research was to assess the impact of adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) and keratinocytes on gelatin/chitosan/β‐glycerol phosphate (GCGP) nanoscaffold in full‐thickness excisional skin wound healing of rats. For this purpose, AD‐MSCs and keratinocytes were isolated from rats and GCGP nanoscaffolds were electrospun. Through an in vivo study, the percentage of wound closure was assessed on days 7, 14, and 21 after wound induction. Samples were taken from the wound sites in order to evaluate the density of collagen fibers and vessels at 7 and 14 days. Moreover, sampling was done on days 7 and 14 from wound sites to assess the density of collagen fibers and vessel...

Research paper thumbnail of CXCR4: A Potential Chemokine Receptor for Future Regenerative Therapeutic Target

Journal of Cell and Molecular Research, 2015

Understanding the molecular mechanisms in regeneration could help the stem cell therapists to imp... more Understanding the molecular mechanisms in regeneration could help the stem cell therapists to improve the clinical practices and could be considered a major milestone in the translation of stem cell research to clinics. Chemokines have been described as one of the most significant singling networks in stem cells homing and regeneration of damaged organs. CXCR4/CXCL12 has been known as a key player in this regard. Expression of CXCR4 has been observed in a number of cells such as mesenchymal stem cells, epithelial cells etc and plays crucial and unique role in the migration of cells towards a cytokine gradient and regulating stem cells trafficking as well as tissue/organ regeneration and embryogenesis.

Research paper thumbnail of Markers of Pluripotency Can be Induced in Human Keratinocytes after Co-culturing with a Pluripotent Tissue

Research paper thumbnail of A New Approach for Optimization of Keratinocyte Culture and Fabrication of Keratinocyte Epidermal Sheets without Using 3T3 Feeder Layer

Research paper thumbnail of Induction of tenogenic differentiation of equine adipose-derived mesenchymal stem cells by platelet-derived growth factor-BB and growth differentiation factor-6

Molecular biology reports, 2020

Managing tendon healing process is complicated mainly due to the limited regeneration capacity of... more Managing tendon healing process is complicated mainly due to the limited regeneration capacity of tendon tissue. Mesenchymal stem cells (MSCs) have potential applications in regenerative medicine and have been considered for tendon repair and regeneration. This study aimed to evaluate the capacity of equine adipose tissue-derived cells (eASCs) to differentiate into tenocytes in response to platelet-derived growth factor-BB (PDGF-BB) and growth differentiation factor-6 (GDF-6) in vitro. Frozen characterized eASCS of 3 mares were thawed and the cells were expanded in basic culture medium (DMEM supplemented with 10% FBS). The cells at passage 5 were treated for 14 days in different conditions including: (1) control group in basic culture medium (CM), (2) induction medium as IM (CM containing L-prolin, and ascorbic acid (AA)) supplemented with PDGF-BB (20 ng/ml), (3) IM supplemented with GDF-6 (20 ng/ml), and (4) IM supplemented with PDGF-BB and GDF-6. At the end of culture period (14th...

Research paper thumbnail of Differentiation of human adipose-derived mesenchymal stem cells toward tenocyte by platelet-derived growth factor-BB and growth differentiation factor-6

Cell and Tissue Banking

Mesenchymal Stem Cells (MSCs) are important in regenerative medicine and tissue engineering and w... more Mesenchymal Stem Cells (MSCs) are important in regenerative medicine and tissue engineering and will be a very sensible choice for repair and regeneration of tendon. New biological practices, such as cellular therapy using stem cells, are promising for facilitating or expediting tendon therapy. Before using these cells clinically, it is best to check and confirm the optimal conditions for differentiation of these cells in the laboratory. Hence, in the present study, the impacts of PDGF-BB and GDF-6 supplementation on adipose-derived MSCs (ASCs) culture were studied. The frozen ASC were recovered and expanded in basic culture medium (DMEM with 10%FBS). The cells after passage five (P5) were treated with basic medium containing L-Prolin, Ascorbic Acid and only PDGF-BB or GDF-6 (20 ng/ml) or both of them (mix) as 3 groups for 14 days to investigate efficiency of ASCs differentiation towards tenocytes. The cells culturing in basic medium were used as control group. To validate tenogenic differentiation, H&E and Sirius Red staining were used to assess cell morphology and collagen production, respectively. In addition, mRNA levels of collagen I and III, Scleraxis and Tenomodulin as tenogenic markers were analyzed using qPCR. In all test groups, cells appeared slenderer, elongated cytoplasmic attributes compared to the control cells. The intensity of Sirius Red staining was significantly higher in GDF-6, PDGF-BB alone, than in group without supplements. The optical density was higher in the GDF-6 than PDGF-BB and mix-group. QPCR results showed that Col I and III gene expression was increased in all groups compared to the control. SCX expression was significantly increased only in the PDGF-BB group. TNMD mRNA expression was not significant among groups. In this study, we have corroborated that human ASCs are reactionary to tenogenic induction by GDF-6 and PDGF-BB alone or in combination. These outcomes will help greater insight into GDF-6 and PDGF-BB driven tenogenesis of ASCs and new directions of discovery in the design of ASC-based treatments for tendon healing.

Research paper thumbnail of Endothelial Cells Derived From Patients With Diabetic Macular Edema Recapitulate Clinical Evaluations of Anti-VEGF Responsiveness Through the Neuronal Pentraxin 2 Pathway

Research paper thumbnail of CRISPR/Cas9 mediated GFP‐human dentin matrix protein 1 (DMP1) promoter knock‐in at the ROSA26 locus in mesenchymal stem cell for monitoring osteoblast differentiation

The Journal of Gene Medicine

Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone, playing a criti... more Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone, playing a critical role in mineralization and phosphate metabolism. One important role for the expression of DMP1 in the nucleus of preosteoblasts is the up‐regulation of osteoblast‐specific genes such as osteocalcin and alkaline phosphatase1. The present study aimed to investigate the potential application of human DMP1 promoter as an indicator marker of osteoblastic differentiation.

Research paper thumbnail of The effect of adrenocorticotropic hormone on alpha‐2‐macroglobulin in osteoblasts derived from human mesenchymal stem cells

Journal of Cellular and Molecular Medicine

Research paper thumbnail of T-Box20 inhibits osteogenic differentiation in adipose-derived human mesenchymal stem cells: the role of T-Box20 on osteogenesis

Journal of Biological Research-Thessaloniki

Background Skeletal development and its cellular function are regulated by various transcription ... more Background Skeletal development and its cellular function are regulated by various transcription factors. The T-box (Tbx) family of transcription factors have critical roles in cellular differentiation as well as heart and limbs organogenesis. These factors possess activator and/or repressor domains to modify the expression of target genes. Despite the obvious effects of Tbx20 on heart development, its impact on bone development is still unknown. Methods To investigate the consequence by forced Tbx20 expression in the osteogenic differentiation of human mesenchymal stem cells derived from adipose tissue (Ad-MSCs), these cells were transduced with a bicistronic lentiviral vector encoding Tbx20 and an enhanced green fluorescent protein. Results Tbx20 gene delivery system suppressed the osteogenic differentiation of Ad-MSCs, as indicated by reduction in alkaline phosphatase activity and Alizarin Red S staining. Consistently, reverse transcription-polymerase chain reaction analyses show...

Research paper thumbnail of Overexpression of MicroRNA-148b-3p stimulates osteogenesis of human bone marrow-derived mesenchymal stem cells: the role of MicroRNA-148b-3p in osteogenesis

Research paper thumbnail of Regeneration and Repair of Skin Wounds: Various Strategies for Treatment

The International Journal of Lower Extremity Wounds

Skin as a mechanical barrier between the inner and outer environment of our body protects us agai... more Skin as a mechanical barrier between the inner and outer environment of our body protects us against infection and electrolyte loss. This organ consists of 3 layers: the epidermis, dermis, and hypodermis. Any disruption in the integrity of skin leads to the formation of wounds, which are divided into 2 main categories: acute wounds and chronic wounds. Generally, acute wounds heal relatively faster. In contrast to acute wounds, closure of chronic wounds is delayed by 3 months after the initial insult. Treatment of chronic wounds has been one of the most challenging issues in the field of regenerative medicine, promoting scientists to develop various therapeutic strategies for a fast, qualified, and most cost-effective treatment modality. Here, we reviewed more recent approaches, including the development of stem cell therapy, tissue-engineered skin substitutes, and skin equivalents, for the healing of complex wounds.

Research paper thumbnail of Adipocyte lineage differentiation potential of MSCs isolated from reaming material

Journal of Cellular Physiology

Mesenchymal stem cells (MSCs) obtained from various sources have been used for different therapeu... more Mesenchymal stem cells (MSCs) obtained from various sources have been used for different therapeutic applications including tissue regeneration. Reamer/irrigator/aspirator (RIA) has been increasingly used in recent years for the derivation of MSCs. Here in this investigation we have comparatively analyzed MSCs obtained from iliac crest bone marrow (ICBM) and RIA for their morphology, cluster determinant (CD) markers, and adipogenic differentiation capacity. MSCs were isolated, cultured, and purified from both sources and then flow cytometric studies were performed to study their characteristics. The differentiation potential of RIA and ICBM was examined by an Oil Red O staining protocol. Moreover, the tissue‐specific markers related to adipogenesis were analyzed by real‐time polymerase chain reaction (RT‐PCR). The cells were cultured in the relevant induction medium and then adipogenic lineage differentiation was tested and confirmed for all MSC preparations. Additionally, analysis by flow cytometer was indicative of RIA derived MSCs (RIA‐MSCs) having a more homogenous population than ICBM derived MSCs. The RIA‐MSCs differentiation toward adipogenic lineage was more efficient compared with ICBM‐MSCs. Direct comparative analysis of RIA to ICBM‐MSCs indicated that the RIA‐MSCs had a higher potential toward adipocyte lineage differentiation compared with ICBM‐MSCs.

Research paper thumbnail of Cancer metastasis versus stem cell homing: Role of platelets

Journal of Cellular Physiology

One of the major obstacles in achieving a successful stem cell therapy is insufficient homing of ... more One of the major obstacles in achieving a successful stem cell therapy is insufficient homing of transplanted cells. To overcome this obstacle, understanding the underlying mechanisms of stem cell homing is of obvious importance. Central to this review is the concept that cancer metastasis can be viewed as a role model to build up a comprehensive concept of stem cell homing. In this novel perspective, the prosurvival choices of the cancerous cells in the bloodstream, their arrest, extravasation, and proliferation at the secondary site can be exploited in favor of targeted stem cell homing. To date, tumor cells have been found to employ a wide variety of strategies to promote metastasis. One of these strategies is through their ability to activate platelets and subsequently activated platelets serve cancer cell survival and metastasis. Accordingly, in the first part of this review the roles of platelets in cancer metastasis as well as stem cell homing are discussed. Next, we provide some lessons learned from cancer metastasis in favor of developing strategies for improvement of stem cell homing with emphasis on the role of platelets. Based on direct or indirect evidence from metastasis, strategies such as manipulation of stem cells to enhance interaction with platelets, preconditioning–pretreatment of stem cells with platelets in vitro, and coinjection of both stem cells and platelets are proposed to improve stem cell homing.

Research paper thumbnail of Using paracrine effects of Ad-MSCs on keratinocyte cultivation and fabrication of epidermal sheets for improving clinical applications

Cell and Tissue Banking

Recent advances in wound healing have made cell therapy a potential approach for the treatment of... more Recent advances in wound healing have made cell therapy a potential approach for the treatment of various types of skin defects such as trauma, burns, scars and diabetic leg ulcers. Cultured keratinocytes have been applied to burn patients since 1981. Patients with acute and chronic wounds can be treated with autologous/allograft cultured keratinocytes. There are various methods for cultivation of epidermal keratinocytes used in cell therapy. One of the important properties of an efficient cell therapy is the preservation of epidermal stem cells. Mesenchymal Stem Cells (MSCs) are major regulatory cells involved in the acceleration of wound healing via induction of cell proliferation, angiogenesis and stimulating the release of paracrine signaling molecules. Considering the beneficial effects of MSCs on wound healing, the main aim of the present study is investigating paracrine effects of Adipose-derived Mesenchymal Stem Cell (Ad-MSCs) on cultivation of keratinocytes with focusing on preservation of stem cells and their differentiation process. We further introduced a new approach for culturing isolated keratinocytes in vitro in order to generate epidermal keratinocyte sheets without using a feeder layer. To do so, Ad-MSC conditioned medium was applied as an alternative to commercial media for keratinocyte cultivation. In this study, the expression of several stem/progenitor cell (P63, K19 and K14) and differentition (K10, IVL and FLG) markers was examined using real time PCR on days 7, 14 and 21 of culture in keratinocytes in Ad-MSC conditioned medium. P63 and α6 integrin expression was also evaluated via flow cytometry. The results were compared with control group including keratinocytes cultured in EpiLife medium and our data indicated that this Ad-MSC conditioned medium is a good alternative for keratinocyte cultivation and producing epidermal sheets for therapeutic and clinical purposes. The reasons are the expression of stem cell and differentiation markers and overcoming the requirement for feeder layer which leads to a xenograft-free transplantation. Besides, this approach has low cost and is easier to perform. However, more in vitro and in vivo experiments as well as safety evaluation required before clinical applications.

Research paper thumbnail of Effect of bioactive glass nanoparticles on biological properties of PLGA/collagen scaffold

Progress in biomaterials, Jan 11, 2018

Bioactive glasses have shown some interesting biological properties such as biocompatibility, bio... more Bioactive glasses have shown some interesting biological properties such as biocompatibility, biodegradation, and angiogenesis in skin tissue engineering. In the current research, the effects of MgO- or CoO-doped 64S bioactive glass with a composition of 64 SiO-26 CaO-5 PO-5 MgO or CoO (mol%) were studied in relation with biological properties of electrospun [poly(lactic-co-glycolic acid) (PLGA)/collagen]. PLGA/collagen samples were rinsed in suspension of bioactive glass nanoparticles in distilled water with a concentration of 0.1 w/v and then freeze dried. Cell adhesion, viability, angiogenesis, and ionic release were performed and tested in culture medium containing fibroblast cells. Attachment and viability of fibroblast cells were increased significantly in bioglass-coated samples, while shrinkage in PLGA/collagen scaffold was reduced by the addition of bioactive glass. Vascular endothelial growth factor secretion in coated scaffold was dropped compared to the uncoated samples....

Research paper thumbnail of Chemically primed bone-marrow derived mesenchymal stem cells show enhanced expression of chemokine receptors contributed to their migration capability

Iranian journal of basic medical sciences, 2016

The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key ob... more The limited homing potential of bone-marrow-derived mesenchymal stem cells (BM-MSC) is the key obstacle in MSC-based therapy. It is believed that chemokines and chemokine receptor interactions play key roles in cellular processes associated with migration. Meanwhile, MSCs express a low level of distinct chemokine receptors and they even lose these receptors on their surface after a few passages which influence their therapeutic applications negatively. This study investigated whether treatment of BM-MSCs with hypoxia-mimicking agents would increase expression of some chemokine receptors and cell migration. BM-MSCs were treated at passage 2 for our gene expression profiling. All qPCR experiments were performed by SYBR Green method in CFX-96 Bio-Rad Real-Time PCR. The Boyden chamber assay was utilized to investigate BM-MSC homing. Possible approaches to increasing the expression level of chemokine receptors by different hypoxia-mimicking agents such as valproic acid (VPA), CoCl2, and ...

Research paper thumbnail of Genetically Modified Human Adipose-Derived Mesenchymal Stem Cells Overexpressing CXCR4R334X, a Hyper Functional Mutant Receptor, Display Enhanced Migration

Research paper thumbnail of Fabrication and mechanical assessment of collagen- polymeric scaffolds prepared by coating and common solvent

Loss of skin can occur for many reasons, including burns and injuries, which in extreme cases can... more Loss of skin can occur for many reasons, including burns and injuries, which in extreme cases can even leads to death. There are different methods for fabrication of scaffolds in tissue engineering such as electrospinning. It seems that use of both natural and synthetic polymers for this purpose could results in better cell adhesion and growth on the electrospun surface. In this study, scaffolds prepared from poly lactic-co-glycolic acid (PLGA), collagen using coating, and common solvents methods. The characteristics of the produced samples evaluated by scanning electron microscopy, porosimetry, infrared spectroscopy and tensile tests. The result of mechanical properties for the scaffold prepared by coating method was far better than scaffold produced from other method and was almost similar to the uncoated PLGA scaffold.