Treadmill running and Levisticum Officinale extract protect against LPS-induced memory deficits by modulating neurogenesis, neuroinflammation and oxidative stress.

Neuroinflammation plays an essential role in the pathogenesis of Alzheimer's disease. The preventive effect of physical exercise on attenuating neuroinflammation has not been completely defined. Levisticum officinale is known as a medicinal plant with antioxidant and anti-inflammatory properties. The current study was designed to investigate the neuroprotective impacts of treadmill running and Levisticum officinale on lipopolysaccharide (LPS)-induced learning and memory impairments and neuroinflammation in rats. Male Wistar rats ran on a treadmill and/or were pretreated with Levisticum officinale extract at a dose of 100 mg/kg for a week. Then, rats received intraperitoneal injection of LPS at a dose of 1 mg/kg. Treadmill running and/or treatment of extract lasted three more weeks. Behavioral, molecular, biochemical and immunohistochemical assessments were carried out after the end of the experiment. LPS administration resulted in spatial learning and memory impairments along with increased mRNA expression of interleukin-6 and malondialdehyde levels, as well as decreased superoxide dismutase activity and neurogenesis in the hippocampus. Moreover, treadmill running for four weeks, alone and in combination with Levisticum officinale extract attenuated spatial learning and memory deficits, decreased the mRNA expression of interleukin-6 and malondialdehyde levels, and enhanced superoxide dismutase activity and neurogenesis in the hippocampus. In conclusion, the advantageous effects of running exercise and Levisticum officinale extract on LPS-induced memory impairments are possibly due to the antioxidant and anti-inflammatory activity and enhancing neurogenesis.

Human adipose derived stem cell exosomes enhance the neural differentiation of PC12 cells.

Human adipose stem cells (hADSCs) are proper cell sources for tissue regeneration. They mainly mediate their therapeutic effects through paracrine factors as exosomes. The exosomes contents are protein, lipid and RNA. Exosomes are effective in restoring the function of neurons and astrocytes in neurodegenerative diseases, and improve the therapeutic outcomes. We investigated the effect of hADSCs derived exosomes on survival and neural differentiation of PC12 cells in vitro. The isolated hADSCs, were characterized by flow cytometry. Exosomes were separated from hADSC-condition medium using Exo-spinTM kit and characterized by DLS and TEM. Then acridine orange staining was performed to confirm entrance of exosomes into PC12 cells. PC12 cells were treated with culture medium containing NGF and exosome. Cell viability was assessed by MTT assay, and neural differentiation by ICC technique and qRT-PCR. TEM and DLS data confirmed the isolation of exosomes according to their size (30-100 nm) and acridine orange staining indicated entrance of exosomes to target cells. MTT assay showed that cell viability was significantly increased in exosome treated group. ICC technique revealed that the expression of Map2 was superior in the exosome treated group. Based on qRT-PCR data, Map2 and ß-tub III gene expression was increased in the exosome treated group. Significant expression of Gfap was seen in the NGF and NGF/EXO treated groups. Present study indicated that hADSCs derived exosomes might enhance cell viability and promote neuronal differentiation and expression of mature neural marker in PC12 cells.

Impact of IFN-ß and LIF overexpression on human adipose-derived stem cells properties.

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells that their therapeutic effects in various diseases make them an interesting tool in cell therapy. In the current study, we aimed to overexpress interferon-ß (IFN-ß) and leukemia inhibitory factor (LIF) cytokines in human ADSCs to evaluate the impact of this overexpression on human ADSCs properties. Here, we designed a construct containing IFN-ß and LIF and then, transduced human adipose-derived stem cells (hADSCs) by this construct via a lentiviral vector (PCDH-513B). We assessed the ability of long-term expression of the transgene in transduced cells by western blot analysis and enzyme-linked immunosorbent assay techniques on Days 15, 45, and 75 after transduction. For the evaluation of stem cell properties, flow cytometry and differentiation assays were performed. Finally, the MTT assay was done to assess the proliferation of transduced cells compares to controls. Our results showed high-efficiency transduction with highest expression rates on Day 75 after transduction which were 70 pg/ml for IFN-ß and 77.9 pg/ml for LIF in comparison with 25.60 pg/ml and 27.63 pg/ml, respectively, in untransduced cells (p = .0001). Also, transduced cells expressed a high level of ADSCs surface markers and successfully differentiated into adipocytes, chondrocytes, neural cells, and osteocytes besides the preservation rate of proliferation near untreated cells (p = .88). All in all, we successfully constructed an hADSC population stably overexpressed IFN-ß and LIF cytokines. Considering the IFN-ß and LIF anti-inflammatory and neuroprotective effects as well as immune-regulatory properties of hADSCs, the obtained cells of this study could be subjected for further evaluations in experimental autoimmune encephalomyelitis mice model.

Therapeutic effects of extracellular vesicles from human adipose-derived mesenchymal stem cells on chronic experimental autoimmune encephalomyelitis.

Since in cell therapy, there are always concerns about immune rejection, genetic disability, and malignancies, special attention has been paid to extracellular vesicles (EVs) which are secreted by mesenchymal stem cells (MSCs). In the present study, we assessed and compared the therapeutic effects of human adipose-derived mesenchymal stem cells (hADSC) and hADSC-EVs from adipose tissue on experimental autoimmune encephalomyelitis (EAE). After induction of EAE in C57Bl/6 mice, they were treated with hADSCs, hADSC-EVs, or vehicle intravenously. The clinical score of all mice was recorded every other day. Mice were killed at Day 30 and splenocytes were isolated for proliferation assay and determination of the frequency of Treg cells by flow cytometry. Leukocyte infiltration by hematoxylin and eosin, percentages of demyelination areas by luxol fast blue, and mean fluorescence intensity of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) by immunohistochemistry were assessed in the spinal cord. Our results showed that the maximum mean clinical score and myelin oligodendrocyte glycoprotein-induced proliferation of splenocytes in hADSC- and hADSC-EV-treated mice were significantly lower than the control mice (p < .05). We also demonstrated that the frequency of CD4+ CD25+ Foxp3+ cells was significantly higher in the spleen of hADSC-treated mice than EAE control mice (p = .023). The inflammation score and the percentages of demyelination areas in hADSC- and hADSC-EV-treated groups significantly declined compared with the untreated control group (p < .05). We also showed that there was no significant difference in MFI of MBP and OLIG2 in the spinal cord of studied groups. Overall, we suggest that intravenous administration of hADSC-EVs attenuates the induced EAE through diminishing proliferative potency of T cells, mean clinical score, leukocyte infiltration, and demyelination in a chronic model of multiple sclerosis.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy.

In recent years, mesenchymal stem/stromal cells (MSCs) have widely been considered as therapeutic tools in basic researches and clinical trials. Accumulating evidence supports the idea that MSCs perform their therapeutic roles in paracrine manner especially through trophic factors and extracellular vesicles (EVs). Compared to cells, EVs have several advantages to be used as therapeutic agents, such as they lack self-replicating capabilities, dangers of ectopic differentiation, and tumor formation, genetic instability, and cellular rejection by the immune system. Since the MSC-derived EVs (MSC-EVs) appear to exert similar therapeutic effects of their parent cells, such as ability to arrive themselves to the site of injury and immunomodulatory properties, MSC-EVs have been widely studied in many animal models, including kidney, liver, cardiovascular, immunological, and neurological diseases. Regarding this, MSC-EVs look to be a novel and interesting approach to be studied in clinical trials of different inflammatory diseases. In this review, we summarize the properties and applications of MSC-EVs in different diseases.

The Story of Nanoparticles in Differentiation of Stem Cells into Neural Cells.

Stem cells have been long looked at as possible therapeutic vehicles in regenerative medicine largely due to their multi-lineage differentiation potential and paracrine actions. Therefore, development of new procedures for the differentiation of stem cells into different cell types holds great potential for opening new opportunities in regenerative medicine. In addition to various methods for inducing stem cell differentiation, the utilization of nanomaterials for differentiation of stem cells has recently received considerable attention and has become a potential tool for such purpose. Multiple lines of evidence revealed that nanomaterial-based scaffolds, inorganic nanoparticles (NPs), and biodegradable polymers have led to significant progress in regulation of stem cell differentiation. Several studies indicated that different NPs including selenium, gold, graphene quantum dots (QDs) and silica could be employed for the regulation of differentiation of stem cells such as human mesenchymal stem cells (hMSCs). In addition, magnetic core-shell NPs could be applied for the regulation of neural stem cell (NSC) differentiation. Taken together, these findings suggested that NPs are potential candidates which could be utilized for the differentiation of stem cells into various cell types such as neural cells. Herein, we summarized the application of NPs for differentiation of stem cells into various cells in particular neural cells.

Therapeutic application of multipotent stem cells.

Cell therapy is an emerging fields in the treatment of various diseases such as cardiovascular, pulmonary, hepatic, and neoplastic diseases. Stem cells are an integral tool for cell therapy. Multipotent stem cells are an important class of stem cells which have the ability to self-renew through dividing and developing into multiple specific cell types in a specific tissue or organ. These cells are capable to activate or inhibit a sequence of cellular and molecular pathways leading to anti-inflammatory and anti-apoptotic effects which might contribute to the treatment of various diseases. It has been showed that multipotent stem cells exert their therapeutic effects via inhibition/activation of a sequence of cellular and molecular pathways. Although the advantages of multipotent stem cells are numerous, further investigation is still necessary to clarify the biology and safety of these cells before they could be considered as a potential treatment for different types of diseases. This review summarizes different features of multipotent stem cells including isolation, differentiation, and therapeutic applications.

MicroRNA: Relevance to stroke diagnosis, prognosis, and therapy.

Stroke is a life-threatening disease that accounts for a considerable burden of mortality in both developing and developed world. Identification of specific biomarkers for stroke and its outcomes can greatly contribute to improved care of patients. MicroRNAs (miRNAs) are known as novel biomarkers that could be used as diagnostic, prognostic, and therapeutic biomarkers. Various studies have shown that miRNAs have key roles in the pathogenesis of stroke, and its complications and outcomes. In addition, there is evidence showing that mesenchaymal stromal cell-derived exosomes containing miRNAs can be used for monitoring and treatment of various diseases such as stroke. Here, we summarized various aspects of miRNA applications in different stages of stroke.

Chronic obstructive pulmonary disease: MicroRNAs and exosomes as new diagnostic and therapeutic biomarkers.

Chronic obstructive pulmonary disease (COPD) is known as a progressive lung disease and the fourth leading cause of death worldwide. Despite valuable efforts, there is still no accurate diagnostic and prognostic tool for COPD. Hence, it seems that finding new biomarkers could contribute to provide better therapeutic platforms for COPD patients. Among various biomarkers, microRNAs (miRNAs) have emerged as new biomarkers for the prognosis and diagnosis of patients with COPD. It has been shown that deregulation of miRNAs targeting a variety of cellular and molecular pathways such as Notch, Wnt, hypoxia-inducible factor-1α, transforming growth factor, Kras, and Smad could be involved in COPD pathogenesis. Multiple lines of evidence have indicated that extracellular vesicles such as exosomes could carry a variety of cargos (i.e., mRNAs, miRNAs, and proteins) which transfer various cellular and molecular signals to recipient cells. Here, we summarized various miRNAs which could be applied as diagnostic and prognostic biomarkers in the treatment of patients with COPD. Moreover, we highlighted the role of extracellular vesicles containing miRNAs as diagnostic and prognostic biomarkers in COPD patients.

Effects of nanozeolite/starch thermoplastic hydrogels on wound healing.

BACKGROUND: Wound healing is a complex biological process. Some injuries lead to chronic nonhealing ulcers, and healing process is a challenge to both the patient and the medical team. We still look forward an appropriate wound dressing. MATERIALS AND METHODS: In this study, starch-based nanocomposite hydrogel scaffolds reinforced by zeolite nanoparticles (nZ) were prepared for wound dressing. In addition, a herbal drug (chamomile extract) was added into the matrix to accelerate healing process. To estimate the cytocompatibility of hydrogel dressings, fibroblast mouse cells (L929) were cultured on scaffolds. Then, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide assay test and interaction of cells and scaffolds were evaluated. For evaluating healing process, 48 male rats were randomly divided into four groups of four animals each (16 rats at each step). The ulcers of the first group were treated with the same size of pure hydrogels. The second group received a bandage with the same size of hydrogel/extract/4 wt% nZ (hydrogel NZE). The third group was treated with chamomile extract, and the fourth group was considered as control without taking any medicament. Finally, the dressings were applied on the chronic refractory ulcers of five patients. RESULTS: After successful surface morphology and cytocompatibility tests, the animal study was carried out. There was a significant difference between starch/extract/4 wt% nZ and other groups on wound size decrement after day 7 (P < 0.05). At the clinical pilot study step, the refractory ulcers of all five patients were healed without any hypersensitivity reaction. CONCLUSION: Starch-based hydrogel/zeolite dressings may be safe and effective for chronic refractory ulcers.

Curcumin: A new candidate for melanoma therapy?

Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin.

Deciphering biological characteristics of tumorigenic subpopulations in human colorectal cancer reveals cellular plasticity.

BACKGROUND: It is supposed that human colorectal cancer consists of a phenotypically distinct population of tumorigenic cancer cells known as cancer stem cells (CSCs) which play a pivotal role in cancer progression, maintenance, metastasis, and the relapse. The aim of this effort was to investigate and compare biological characterizations of CD133+ with CD133- cell subsets isolated from both primary and metastatic human colorectal tumors. MATERIALS AND METHODS: Using our optimized protocols, unfixed colorectal tumors were enzymatically and mechanically dissociated into single cells followed by evaluation of postdigestion viability. The obtained single cell suspensions were then subjected to cell sorting using magnetic beads according to CD133 marker. The resultant CD133+ and CD133- cell subsets were cultured in specific cell culture medium followed by aldehyde dehydrogenases (ALDH) activity assessment and flow cytometric analyses. RESULTS: The results demonstrate that CD133+ cells have smaller size and lower complexity of intracellular structure, sphere formation ability, and ALDH enzyme activity while CD133- cells isolated from primary colon cancer samples were not able to form a sphere and did not show ALDH enzyme activity. Intriguingly, CD133- cells isolated from metastatic colorectal cancer specimen were able to form a sphere and shown ALDH enzyme activity. The present study indicates that our results are in agreement with SC theory and possibility of the existence of cellular plasticity among cancer subpopulations should be portrayed. CONCLUSION: We also conclude that this cellular plasticity is greatly affected by tumor microenvironment cues and the role of CSCs niche in cancer therapeutic strategies should be precisely considered.

Fabrication and properties evaluation of chitosan/BaTiO3 composite membranes for the periodontitis treatment.

Periodontitis gradually damages the hard and soft tissues surrounding the tooth, leading to tooth loss. In recent years, the use of biomaterials in periodontitis treatment has expanded, including gels, nanoparticles, microparticles, fibers, and membranes. Among these, membranes have more clinical applications. Due to the ability of the piezoelectric material to regenerate damaged tissues, the aim of this study was to create piezoelectric composite membranes. To achieve this, Barium titanate powder (BaTiO3 powder)-a piezoelectric substance-was synthesized using the hydrothermal method and analyzed with X-ray diffraction (XRD) and Field emission scanning electron microscopy (FESEM). Four types of membranes were fabricated using solvent casting method: three composite membranes with chitosan matrix and BaTiO3 fillers (at 3%, 6%, and 9% weight), and one chitosan membrane without BaTiO3. The microstructure of the membrane surfaces, agglomeration of BaTiO3 in membranes, and hydrophilicity, antibacterial, and electrical properties of the membrane were also investigated. The results indicated that membranes containing 3 and 6% BaTiO3 had suitable surface structure for the periodontitis treatment. Agglomeration of BaTiO3 particles was higher in the membrane containing 9% BaTiO3. The large amount of BaTiO3 improved the antibacterial properties of the membranes. Additionally, the membranes containing BaTiO3 had high electrical properties, especially those with 3% and 6% BaTiO3. Therefore, composite membranes containing BaTiO3, especially membranes containing 6% BaTiO3, are more favorable options than those without BaTiO3 for periodontitis treatment.

3D printed polylactic acid-based nanocomposite scaffold stuffed with microporous simvastatin-loaded polyelectrolyte for craniofacial reconstruction.

Critical sized craniofacial defects are among the most challenging bone defects to repair, due to the anatomical complexity and aesthetic importance. In this study, a polylactic acid/hardystonite-graphene oxide (PLA/HTGO) scaffold was fabricated through 3D printing. In order to upgrade the 3D printed scaffold to a highly porous scaffold, its channels were filled with pectin-quaternized chitosan (Pec-QCs) polyelectrolyte solution containing 0 or 20 mg/mL of simvastatin (Sim) and then freeze-dried. These scaffolds were named FD and FD-Sim, respectively. Also, similar PLA/HTGO scaffolds were prepared and dip coated with Pec-QCs solution containing 0 or 20 mg/mL of Sim and were named DC and DC-Sim, respectively. The formation of macro/microporous structure was confirmed by morphological investigations. The release of Sim from DC-Sim and FD-Sim scaffolds after 28 days was measured as 77.40 ± 5.25 and 86.02 ± 3.63 %, respectively. Cytocompatibility assessments showed that MG-63 cells had the highest proliferation, attachment and spread on the Sim containing scaffolds, especially FD-Sim. In vivo studies on a rat calvarial defect model revealed that an almost complete recovery occurred in the group treated with FD-Sim scaffold after 8 weeks and the defect was filled with newly formed bone. The results of this study acknowledge that the FD-Sim scaffold can be a perfect candidate for calvarial defect repair.

Retraction notice to "The therapeutic potential of human adipose-derived mesenchymal stem cells producing CXCL10 in a mouse melanoma lung metastasis model" [Cancer Lett. 419 (2018) 30-39].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After publication, the Editors were contacted by a concerned reader regarding alleged image duplication. These allegations are in regard to Fig. 3a being duplicated from a previously published paper in the journal Stem Cells (Stem Cells. 2008 Sep;26 (9):2332-8. doi: 10.1634/stemcells.2008-0084) and Fig. 8a being duplicated from a previously published paper in the journal Molecular Cancer (Mol Cancer 13, 255 (2014). https://doi.org/10.1186/1476-4598-13-255). After a thorough investigation by the editorial team, the Editors determined that there are multiple identical details between Fig. 5A (Cancer Letters) and Fig. 3A (Stem Cells) and the authors did not produce satisfactory evidence that the published images in Cancer Letters were original. Due to this, the Editor does not have confidence in the results and conclusions presented and has made the decision to retract.

Morphology-Dependent Immunomodulatory Coating of Hydroxyapatite/PEO for Magnesium-Based Bone Implants.

One of the most critical issues concerning orthopedic implants is the risk of chronic inflammation, which poses a threat to the bone healing process. Osteo-immunomodulation plays a pivotal role in implant technology by influencing proinflammatory and anti-inflammatory responses, ultimately promoting bone healing. This study aims to investigate the morphology-dependent osteo-immunomodulatory properties of a hydroxyapatite (HA)/plasma electrolytic oxidation (PEO)-coated WE43 alloy. In this context, following the PEO process with various operational parameters (duty cycles of 50-40, 50-20, 70-40%, and frequencies of 0.5, 0.8, and 1 kHz), a layer of HA was applied as the top coating using a straightforward hot-dip process. The results revealed the formation of the PEO layer with distinct morphologies and pore sizes, depending on the operational parameters. Specifically, a uniform PEO coating with small pore sizes (5.2-5.3 µm) led to the creation of plate-like HA particles, while a random-like HA structure formed on nonuniform surfaces with large pores (7.0-11.1 µm) of PEO. Moreover, it was observed that the plate-like HA coating exhibited higher adhesion strength than the random one (classified as class 2 vs class 3 based on cross-cut standards). Furthermore, electrochemical impedance spectroscopy (EIS) and polarization studies confirmed a substantial increase in the polarization resistance (680 kΩ) and total impedance (48 559.6 Ω) for the plate-like HA/PEO as compared to the substrate (an increase of 1511-fold and 311-fold, respectively) and the random HA/PEO samples (an increase of 85-fold and 18-fold, respectively). In addition, compared to random HA coatings, there was a significant enhancement in the viability (150% control vs 96% control), proliferation, and differentiation of MG63 cells when exposed to plate-like HA coatings. Moreover, surface morphology and chemistry pronouncedly impacted macrophages' viability, morphology, and phenotype. Notably, plate-like HA coatings resulted in a higher upregulation of BMP-2 and TGF-ß than proinflammatory cytokines (IL-6 and M-CSF), indicating a polarization of macrophage type 1 (M1) toward type 2 (M2). In summary, the bilayer HA/PEO coating exhibited remarkable osteo-immunomodulatory activity, making it highly appealing for use in bone implant applications.

Incorporation of graphene oxide as a coupling agent in a 3D printed polylactic acid/hardystonite nanocomposite scaffold for bone tissue regeneration applications.

3D printing fabrication has become a dominant approach for the creation of tissue engineering constructs as it is accurate, fast, reproducible and can produce patient-specific templates. In this study, 3D printing is applied to create nanocomposite scaffold of polylactic acid (PLA)/hardystonite (HT)-graphene oxide (GO). GO is utilized as a coupling agent of alkaline treated HT nanoparticles within PLA matrix. The addition of HT-GO nanoparticles of up to 30 wt% to PLA matrix was found to increase the degradability from 7.33 ± 0.66 to 16.03 ± 1.47 % during 28 days. Also, the addition of 20 wt% of HT-GO nanoparticles to PLA scaffold (PLA/20HTGO sample) significantly increased the compressive strength (from 7.65 ± 0.86 to 14.66 ± 1.01 MPa) and elastic modulus (from 94.46 ± 18.03 to 189.15 ± 10.87 MPa). The apatite formation on the surface of nanocomposite scaffolds in simulated body fluid within 28 days confirmed the excellent bioactivity of nanocomposite scaffolds. The MG63 cell adhesion and proliferation and, also, the rat bone marrow mesenchymal stem cells osteogenic differentiation were highly stimulated on the PLA/20HTGO scaffold. According to the sum of results obtained in the current study, the optimized PLA/20HTGO nanocomposite scaffold is highly promising for hard tissue engineering applications.

An animal model study of osteochondral defect repair by human adipose stem cells and pomegranate fruit hydroalchoholic extract.

Objective: Articular cartilage damages do not repair spontaneously. Tissue engineering is a promising approach to repair cartilage damage. Transforming growth factor-beta (TGF-ß) members are the known induction factors in chondrogenic differentiation. However, hypertrophy of the chondrocytes resulting from mesenchymal stem cells (MSCs) induction by TGF-ß is inevitable. Pomegranate fruit contains many ingredients which are useful in ensuring the health of organs. This study was designed to investigate the Pomegranate Fruit hydroalchoholic Extract (PFE) capability in human adipose derived stem cells (hASCs) differentiation into the chondrocytes on fibrin scaffold. Materials and Methods: Pomegranate fruit hydroalchoholic extract (PFE) was prepared. hASCs were isolated, expanded, labeled, and seeded on the fibrin scaffold. The constructs were divided into three groups including TGF-ß3, PFE, and control. The constructs were induced for 14 days, then, the MTT assay, Real-Time Polymerase Chain Reaction (PCR), and histochemistry assessments were run, and finally, the constructs were transplanted into the knee defect of rats. The gross and histological assessments of the transplants were done after 8 weeks. Results: The viability rate, COL2A1, Aggrecan (ACAN) and COL10A1 genes expression levels, and histological criterion of the PFE samples were significantly higher than that of the control. The macroscopic grades and histological results of the PFE samples were close to that of the TGF-ß3. The number of positive cells for COLІI protein were higher significantly in the PFE group than the control. Conclusion: PFE was effective in the chondrogenic induction of hASCs. Further studies are needed to find out the events of the chondrogenic induction using PFE.

Development of an electrospun poly(ε-caprolactone)/collagen-based human amniotic membrane powder scaffold for culturing retinal pigment epithelial cells.

The common retinal diseases are age-related macular degeneration (AMD) and retinitis pigmentosa (RP). They are usually associated with the dysfunction of retinal pigment epithelial (RPE) cells and degeneration of underlying Bruch's membrane. The RPE cell transplantation is the most promising therapeutic option to restore lost vision. This study aimed to construct an ultrathin porous fibrous film with properties similar to that of native Bruch's membrane as carriers for the RPE cells. Human amniotic membrane powder (HAMP)/Polycaprolactone (PCL) scaffolds containing different concentrations of HAMP were fabricated by electrospinning technique. The results showed that with increasing the concentration of HAMP, the diameter of fibers increased. Moreover, hydrophilicity and degradation rate were improved from 119° to 92° and 14 to 56% after 28 days immersion in phosphate-buffered saline (PBS) solution, respectively. All scaffolds had a porosity above 85%. Proper cell adhesion was obtained one day after culture and no toxicity was observed. However, after seven days, the rate of growth and proliferation of ARPE-19 cells, a culture model of RPE, on the PCL-30HAMP scaffold (HAMP concentration in PCL 7.2% by weight) was higher compared to other scaffolds. These results indicated that PCL-30HAMP fibrous scaffold has a great potential to be used in retinal tissue engineering applications.