Sharif Digital Repository

Graphene nanogrids (crossed graphene nanoribbons synthesized by the oxidative unzipping of multi-walled carbon nanotubes) on a SiO2 matrix containing TiO2 nanoparticles (NPs) were applied as a photocatalytic stimulator in the accelerated differentiation of human neural stem cells (hNSCs) into two-dimensional neural networks. The hydrophilic graphene nanogrids exhibited patterned proliferations of hNSCs (consistent with patterns of the nanogrids), in contrast with the usual random growths occurring on quartz substrates. The number of cell nuclei differentiated on reduced graphene oxide nanoribbon (rGONR) grid/TiO2 NPs/SiO2 increased ∼5.9 and 26.8 fold compared to the number of cells on quartz... 

Development of novel engineering techniques that can promote new clinical treatments requires implementing multidisciplinary in-vitro and in-vivo approaches. In this study, we have implemented microfluidic devices and in-vivorat model to study the mechanism of neural stem cell migration and differentiation.These studies can result in the treatment of damages to the neuronal system. In this research, we have shown that by applying appropriate ranges of biochemical and biomechanical factors as well as by exposing the cells to electromagnetic fields, it is possible to improve viability, proliferation, directional migration and differentiation of neural stem cells. The results of this study can... 

In serial passaging cultures of mouse embryonic stem (ES) cells, we employed a dendrimer-immobilized substrate that displayed D-glucose as a terminal ligand. The D-glucose-displaying dendrimer (GLU/D) surface caused the ES cells to form loosely attached spherical colonies, while those on a gelatin-coated surface formed flatter colonies that were firmly attached to the surface. Despite the morphological similarities between the colonies on the GLU/D surface and aggregates on a conventional bacteriological dish, immunostaining and RT-PCR analyses revealed the maintenance of cells within the spherical colonies on the GLU/D surface in an undifferentiated state with very low expressions of... 

Cells can sense and respond to changes in the topographical, chemical, and mechanical information in their environment. Engineered substrates are increasingly being developed that exploit these physical attributes to direct cell responses (most notably mesenchymal stem cells) and therefore control cell behavior toward desired applications. However, there are very few methods available for robust and accurate modeling that can predict cell behavior prior to experimental evaluations, and this typically means that many cell test iterations are needed to identify best material features. Here, we developed a unifying computational framework to create a multicomponent cell model, called the... 

Despite the promise of hydrogel-based stem cell therapies in orthopedics, a significant need still exists for the development of injectable microenvironments capable of utilizing the regenerative potential of donor cells. Indeed, the quest for biomaterials that can direct stem cells into bone without the need of external factors has been the "Holy Grail" in orthopedic stem cell therapy for decades. To address this challenge, we have utilized a combinatorial approach to screen over 63 nanoengineered hydrogels made from alginate, hyaluronic acid, and two-dimensional nanoclays. Out of these combinations, we have identified a biomaterial that can promote osteogenesis in the absence of... 

In this study, a novel biodegradable hyaluronic acid (HA) based microgel were prepared via enzymatic crosslinking of tyramine conjugated HA (HA-TA) in an inverse microemulsion. HA-TA microdroplets were crosslinked within a few seconds in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ). The high water content of the polymeric network and the inherent negative charge of the HA-TA microgels provided a suitable platform for encapsulation of cationic proteins like lysozyme and TGF-β1 growth factor. The results demonstrated that lysozyme was released, after an initial burst release, in a suitable sustained manner over a period of four weeks. Both diffusion and... 

For the application of human neural stem cells (hNSCs) in neural regeneration and brain repair, it is necessary to stimulate hNSC differentiation towards neurons rather than glia. Due to the unique properties of graphene in stem cell differentiation, here we introduce reduced graphene oxide (rGO)/TiO2 heterojunction film as a biocompatible flash photo stimulator for effective differentiation of hNSCs into neurons. Using the stimulation, the number of cell nuclei on rGO/TiO2 increased by a factor of ∼1.5, while on GO/TiO2 and TiO2 it increased only ∼48 and 24%, respectively. Moreover, under optimum conditions of flash photo stimulation (10 mW cm-2 flash intensity and 15.0 mM ascorbic acid in... 

The present study analyzed the dose-dependent cyto- and genotoxicity of graphene oxide and reduced graphene oxide on spermatogonial stem cells (SSCs) for the first time. The results showed that graphene oxide significantly increased oxidative stress at concentrations of 100 and 400 μg/ml, while low concentrations did not have a significant effect. In addition, according to the MTT assay, the cell number decreased in high-concentration (100 and 400 μg/ml) graphene oxide-treated samples compared to untreated cells. However, a reduced graphene-treated sample demonstrated a significant increase in cell number. Moreover, microscopic analysis found high concentrations of graphene nanosheets in... 

A combination of topographical cues and controlled release of biochemical factors is a potential platform in controlling stem cells differentiation. In this study the synergistic effect of nanotopography and sustained release of biofunctional transforming growth factor beta 1 (TGF-β1) on differentiation of human Wharton's Jelly-derived mesenchymal stem cell (hWJ-derived UC-MSCs) toward myogenic lineage was investigated. In order to achieve a sustained release of TGF-β1, this factor was encapsulated within chitosan nanoparticles. Afterwards the aligned composite mats were fabricated using poly-E-caprolacton (PCL) containing TGF-β1-loaded chitosan nanoparticles and poly-L-lactic acid (PLLA).... 

Single-layer reduced graphene oxide nanoribbons (rGONRs) were obtained through an oxidative unzipping of multi-walled carbon nanotubes and a subsequent deoxygenation by hydrazine and bovine serum albumin. Human mesenchymal stem cells (hMSCs) were isolated from umbilical cord blood and used for checking the concentration- and time-dependent cyto- and geno-toxic effects of the rGONRs and reduced graphene oxide sheets (rGOSs). The cell viability assay indicated significant cytotoxic effects of 10 μg/mL rGONRs after 1 h exposure time, while the rGOSs exhibited the same cytotoxicity at concentration of 100 μg/mL after 96 h. The oxidative stress was found as the main mechanism involved in the... 

In this study, we reported the preparation of self cross-linked oxidized alginate-gelatin hydrogels for muscle tissue engineering. The effect of oxidation degree (OD) and oxidized alginate/gelatin (OA/GEL) weight ratio were examined and the results showed that in the constant OA/GEL weight ratio, both cross-linking density and Young's modulus enhanced by increasing OD due to increment of aldehyde groups. Furthermore, the degradation rate was increased with increasing OD probably due to decrement in alginate molecular weight during oxidation reaction facilitated degradation of alginate chains. MTT cytotoxicity assays performed on Wharton's Jelly-derived umbilical cord mesenchymal stem cells... 

Producing mature and functional cardiomyocytes (CMs) by in vitro differentiation of induced pluripotent stem cells (iPSCs) using only biochemical cues is challenging. To mimic the biophysical and biomechanical complexity of the native in vivo environment during the differentiation and maturation process, polydimethylsiloxane substrates with 3D topography at the micrometer and sub-micrometer levels are developed and used as cell-culture substrates. The results show that while cylindrical patterns on the substrates resembling mature CMs enhance the maturation of iPSC-derived CMs, sub-micrometer-level topographical features derived by imprinting primary human CMs further accelerate both the... 

The simultaneous effect of electrospun scaffold alignment and polymer composition on chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSC) is investigated. Aligned and randomly oriented polycaprolactone/poly(lactic-co-glycolic acid) (PLGA) hybrid electrospun scaffolds with two different ratios are fabricated by electrospinning. It is found that aligned nanofibrous scaffolds support higher chondrogenic differentiation of hBMMSCs compared to random ones. The aligned scaffolds show a higher expression level of chondrogenic markers such as type II collagen and aggrecan. It is concluded that the aligned nanofibrous scaffold with higher PLGA ratio could significantly... 

A large number of treatment approaches have been used for spinal cord injury improvement, a medically incurable disorder, and subsequently stem cell transplantation appears to be a promising strategy. The main objective of this study is to ascertain whether combinational therapy of human neural stem cells (hNSCs) together with lithium chloride improves cell survival, proliferation, and differentiation in a rat spinal contusion model, or not. Contusive spinal cord injury was implemented on Wistar male rats. Experimental groups comprised of: control, hNSCs transplanted, lithium chloride (Li), and hNSCs and lithium chloride (hNSCs + Li). In every experimental group, locomotor activity score and... 

Three-dimensional cell culture and the forming multicellular aggregates are superior over traditional monolayer approaches due to better mimicking of in vivo conditions and hence functions of a tissue. A considerable amount of attention has been devoted to devising efficient methods for the rapid formation of uniform-sized multicellular aggregates. Microfluidic technology describes a platform of techniques comprising microchannels to manipulate the small number of reagents with unique properties and capabilities suitable for biological studies. The focus of this review is to highlight recent studies of using microfluidics, especially droplet-based types for the formation, culture, and... 

Background: Recent clinical studies of treating traumatic brain injury (TBI) with autologous adult stem cells led us to compare effect of intravenous injection of bone marrow mesenchymal stem cells (BMSC) and bone marrow hematopoietic stem cell mobilization, induced by granulocyte colony stimulating factor (G-CSF), in rats with a cortical compact device. Methods: Forty adult male Wistar rats were injured with controlled cortical impact device and divided randomly into four groups. The treatment groups were injected with 2 × 106 intravenous bone marrow stromal stem cell (n = 10) and also with subcutaneous G-CSF (n = 10) and sham-operation group (n = 10) received PBS and "bromodeoxyuridine... 

Background: Researchers are trying to study the mechanism of neural stem cells (NSCs) differentiation to oligodendrocyte-like cells (OLCs) as well as to enhance the selective differentiation of NSCs to oligodendrocytes. However, the limitation in nerve tissue acces-sibility to isolate the NSCs as well as their differentiation toward oligodendrocytes is still challenging. Purpose: In the present study, a hybrid polycaprolactone (PCL)-gelatin nanofiber scaffold mimicking the native extracellular matrix and axon morphology to direct the differentiation of bone marrow-derived NSCs to OLCs was introduced. Materials and Methods: In order to achieve a sustained release of T3, this factor was...