Combination Therapy of Stem Cell-derived Exosomes and Biomaterials in the Wound Healing.

Wound healing is a serious obstacle due to the complexity of evaluation and management. While novel approaches to promoting chronic wound healing are of critical interest at the moment, several studies have demonstrated that combination therapy is critical for the treatment of a variety of diseases, particularly chronic wounds. Among the various approaches that have been proposed for wound care, regenerative medicine-based methods have garnered the most attention. As is well known, regenerative medicine's three primary tools are gene/cell therapy, biomaterials, and tissue engineering. Multifunctional biomaterials composed of synthetic and natural components are highly advantageous for exosome carriers, which utilizing them is an exciting wound healing method. Recently, stem cell-secreted exosomes and certain biomaterials have been identified as critical components of the wound healing process, and their combination therapy appears to produce significant results. This paper presents a review of literature and perspectives on the use of stem cell-derived exosomes and biomaterials in wound healing, particularly chronic wounds, and discusses the possibility of future clinical applications.

Stem Cell Therapy Potency in Personalizing Severe COVID-19 Treatment.

Currently, there are no specific and efficient vaccines or drugs for COVID-19, particularly in severe cases. A wide range of variations in the clinical symptoms of different patients attributed to genomic differences. Therefore, personalized treatments seem to play a critical role in improving these symptoms and even similar conditions. Prompted by the uncertainties in the area of COVID-19 therapies, we reviewed the published papers and concepts to gather and provide useful information to clinicians and researchers interested in personalized medicine and cell-based therapy. One novel aspect of this study focuses on the potential application of personalized medicine in treating severe cases of COVID-19. However, it is theoretical, as any real-world examples of the use of genuinely personalized medicine have not existed yet. Nevertheless, we know that stem cells, especially MSCs, have immune-modulatory effects and can be stored for future personalized medicine applications. This theory has been conjugated with some evidence that we review in the present study. Besides, we discuss the importance of personalized medicine and its possible aspects in COVID-19 treatment, then review the cell-based therapy studies for COVID-19 with a particular focus on stem cell-based therapies as a primary personalized tool medicine. However, the idea of cell-based therapy has not been accepted by several scientific communities due to some concerns of lack of satisfactory clinical studies; still, the MSCs and their clinical outcomes have been revealed the safety and potency of this therapeutic approach in several diseases, especially in the immune-mediated inflammatory diseases and some incurable diseases. Promising outcomes have resulted in that clinical studies are going to continue.

Metformin-Loaded PCL/PVA Fibrous Scaffold Preseeded with Human Endometrial Stem Cells for Effective Guided Bone Regeneration Membranes.

Many studies have been devoted to investigating the potential of guided bone regeneration (GBR) membranes for bone defect reconstruction. Regardless of approaches for treating damaged bone tissues, a beneficial therapeutic strategy has remained a challenge. In this study, a novel GBR membrane with polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) containing different concentrations of metformin (Met) for improving osteogenic properties was developed. The membranes were evaluated for their hydrophilicity, degradation rate, swelling ratio, drug release, mechanical properties, and biological responses. The results showed a significant increase in hydrophilicity, swelling ratio, and degradation rate and no significant changes in mechanical properties of PCL/PVA membranes with Met concentration enhancement. A decrease in cell viability cultured on the surface of the PCL/PVA membrane was seen when the amount of Met was changed from 10 to 15 wt %. The results of the in vitro quantitative real-time polymerase chain reaction (qRT-PCR) also confirmed the higher secretion of osteogenic-related genes in a PCL/PVA/Cell/10 wt % Met scaffold than in the PCL/PVA/Cell sample. Therefore, further in vivo studies were conducted using the electrospun PCL/PVA membrane containing human endometrial stem cells (hEnSCs) and 10% Met. Histopathological and histomorphometric results confirmed that PCL/PVA/hEnSCs/10 wt % Met has excellent potential to differentiate hEnSCs into osteogenic lineages and bone regeneration in calvarial defects of rats. The results of this study confirm the high potential of the PCL/PVA/10 wt % Met fibrous membrane preseeded with hEnSCs in GBR applications.

Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises.

Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19. Graphical Abstract Therapeutic Potential of Regenerative Medicine against COVID19.

Microfluidic devices for detection of RNA viruses.

There is a long way to go before the coronavirus disease 2019 (Covid-19) outbreak comes under control. qRT-PCR is currently used for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Covid-19, but it is expensive, time-consuming, and not as sensitive as it should be. Finding a rapid, easy-to-use, and cheap diagnostic method is necessary to help control the current outbreak. Microfluidic systems provide a platform for many diagnostic tests, including RT-PCR, RT-LAMP, nested-PCR, nucleic acid hybridization, ELISA, fluorescence-Based Assays, rolling circle amplification, aptamers, sample preparation multiplexer (SPM), Porous Silicon Nanowire Forest, silica sol-gel coating/bonding, and CRISPR. They promise faster, cheaper, and easy-to-use methods with higher sensitivity, so microfluidic devices have a high potential to be an alternative method for the detection of viral RNA. These devices have previously been used to detect RNA viruses such as H1N1, Zika, HAV, HIV, and norovirus, with acceptable results. This paper provides an overview of microfluidic systems as diagnostic methods for RNA viruses with a focus on SARS-CoV-2.

Defining the role of 17ß-estradiol in human endometrial stem cells differentiation into neuron-like cells.

Human endometrial stem cells (hEnSCs) that can be differentiated into various neural cell types have been regarded as a suitable cell population for neural tissue engineering and regenerative medicine. Considering different interactions between hormones, growth factors, and other factors in the neural system, several differentiation protocols have been proposed to direct hEnSCs towards specific neural cells. The 17ß-estradiol plays important roles in the processes of development, maturation, and function of nervous system. In the present research, the impact of 17ß-estradiol (estrogen, E2) on the neural differentiation of hEnSCs was examined for the first time, based on the expression levels of neural genes and proteins. In this regard, hEnSCs were differentiated into neuron-like cells after exposure to retinoic acid (RA), epidermal growth factor (EGF), and also fibroblast growth factor-2 (FGF2) in the absence or presence of 17ß-estradiol. The majority of cells showed a multipolar morphology. In all groups, the expression levels of nestin, Tuj-1 and NF-H (neurofilament heavy polypeptide) (as neural-specific markers) increased during 14 days. According to the outcomes of immunofluorescence (IF) and real-time PCR analyses, the neuron-specific markers were more expressed in the estrogen-treated groups, in comparison with the estrogen-free ones. These findings suggest that 17ß-estradiol along with other growth factors can stimulate and upregulate the expression of neural markers during the neuronal differentiation of hEnSCs. Moreover, our findings confirm that hEnSCs can be an appropriate cell source for cell therapy of neurodegenerative diseases and neural tissue engineering.

Cartilage tissue formation from human adipose-derived stem cells via herbal component (Avocado/soybean unsaponifiables) in scaffold-free culture system.

BACKGROUND: The use of stem cells, growth factors, and scaffolds to repair damaged tissues is a new idea in tissue engineering. The aim of the present study is the investigation of Avocado/soybean (A/S) effects on chondrogenic differentiation of human adipose-derived stem cells (hADSCs) in micromass culture to access cartilage tissue with high quality. MATERIALS AND METHODS: In this an experimental study After hADSCs characterization, chondrogenic differentiation was induced using transforming growth factor beta 1 (TGF-ß1) (10 ng/ml) and different concentrations (5, 10, and 20 µg/ml) of A/S in micromass culture. The efficiency of A/S on specific gene expression (types I, II, and X collagens, SOX9, and aggrecan) was evaluated using quantitative polymerase chain reaction. In addition, histological study was done using hematoxylin and eosin and toluidine blue staining all data were analyzed using one-way analysis of variance (ANOVA) and P ≤ 0.05 was considered to be statistically significant. RESULTS: The results of this study indicated that A/S can promote chondrogenic differentiation in a dose-dependent manner. In particular, 5 ng/ml A/S showed the highest expression of type II collagen, SOX9, and aggrecan which are effective and important markers in chondrogenic differentiation. In addition, the expression of types I and X collagens which are hypertrophic and fibrous factors in chondrogenesis is lower in present of 5 ng/ml A/S compared with TGF-ß1 group (P ≤ 0.05). Moreover, the sulfated glycosaminoglycans in the extracellular matrix and the presence of chondrocytes within lacuna were more prominent in 5 ng/ml A/S group than other groups. CONCLUSION: It can be concluded that A/S similar to TGF-ß1 is able to facilitate the chondrogenic differentiation of hADSCs and do not have adverse effects of TGF-ß1. Thus, TGF-ß1 can be replaced by A/S in the field of tissue engineering.

Microtubule stabilizer epothilone B as a motor neuron differentiation agent for human endometrial stem cells.

Microtubule-stabilizing agents (MSAs), until now, have primarily been considered for their anti-proliferative effects in the setting of cancer. However, recent studies have revealed that one particular MSA, epothilone B (EpoB), can promote axonal regeneration after traumatic spinal cord injuries (SCI) even in the presence of inhibitor molecules such as neurite outgrowth inhibitor-A (Nogo-A). On the basis of the importance of having an efficient motor neuron (MN) differentiation protocol for stem cell therapy and the attention of MSAs for SCI treatment, our study investigated the effect of EpoB on human endometrial stem cells (hEnSCs) differentiation into MN-like cells. hEnSCs were isolated and characterized by flow cytometry. The hEnSC cell viability was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To mimic the in vivo inhibitory environment, hEnSCs were also differentiated in the presence of Nogo-A. After 15 days of differentiation, the expressions of MN-markers were evaluated by real-time reverse-transcriptase polymerase chain reaction and immunofluorescence. According to the MTT assay results, three doses (1, 5, and 10 nM) of EpoB were selected to evaluate their effect on MN-differentiation. All selected doses can increase the efficacy of hEnSCs differentiation into MN-like cells. In particular, the 10 nM EpoB dosage was shown to increase the axon elongation, cell alignment, and upregulation of these MN-markers compared with other doses. EpoB can improve MN differentiation from hEnSC and potentially provide a unique route for neuronal replacement in the setting of SCI.

A silk fibroin/decellularized extract of Wharton's jelly hydrogel intended for cartilage tissue engineering.

A hybrid hydrogel was obtained from decellularized extract from Wharton's jelly (DEWJ) and silk fibroin (SF) and characterized for cartilage tissue engineering. Wharton's jelly was used due to its similarity with articular cartilage in extracellular matrix composition. Also, silk fibroin has good mechanical properties which make this construct appropriate for cartilage repair. Decellularization of Wharton's jelly was verified by DAPI staining, DNA quantification, and PCR analysis. Then, the biochemical composition of DEWJ was determined by ELISA kits for total proteins, collagens, sulfated glycosaminoglycans (sGAG), and transforming growth factor ß1 (TGF-ß1). After fabricating pure SF and SF/DEWJ hybrid hydrogels, their physical and mechanical properties were characterized by FESEM, Fourier-transform infrared spectroscopy (FTIR) and rheological assays (amplitude and frequency sweeps). Furthermore, cell viability and proliferation were assessed by MTT assay. The results have shown that DEWJ in hybrid hydrogels enhances mechanical properties of the construct relative to pure SF hydrogels. Also, this extract at its 40% concentration in culture media and 20% or 40% concentrations in SF/DEWJ hybrid hydrogels significantly increases population of the cells compared to control and pure SF hydrogel after 7 days. In conclusion, this study proposes the potential of SF/DEWJ hybrid hydrogels for cartilage tissue engineering applications.

Preparation of fibrin gel scaffolds containing MWCNT/PU nanofibers for neural tissue engineering.

Compared to the peripheral nervous system, in the central nervous system (CNS) disorders, neurons are less able to regenerate and reconstruct the neural tissue. Tissue engineering is considered as a promising approach for neural regeneration and restoring neurologic function after CNS injuries. Nanofibrous hydrogels have been recently used as three-dimensional (3D) scaffolds for tissue engineering applications. In this kind of composites, hydrogels are incorporated with fibers to enhance their poor mechanical properties. Furthermore, introducing meshes within hydrogels can result in composites associated with advantages of both components. In the present study, we have prepared 3D nanofibrous hydrogel scaffolds based on fibrin/polyurethane/multiwall carbon nanotube (fibrin/PU/MWCNT), for application as composite scaffolds for neural tissue engineering. The fabricated fibrin/PU/MWCNT hydrogel scaffolds were characterized and their ability to support cell attachment and viability was assessed in comparison with fibrin hydrogel. Scanning electron microscopy (SEM) analysis was performed to examine the microstructural features of scaffolds. The rate of biodegradation and rheological properties of scaffolds were also investigated. After isolation of human endometrial stem cells (hEnSCs), they were cultured into the scaffolds, then their attachment and viability were assessed through SEM analysis, MTT assay and DAPI staining. Based on the results, the viability and proliferation of hEnSCs in the fibrin/PU/MWCNT hydrogels were higher than those in fibrin hydrogels. Therefore, our novel fabricated fibrin/PU/MWCNT hydrogel is able to support cell proliferation and can be used as a scaffold to provide an appropriate microenvironment for enhancing cell viability. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 802-814, 2019.