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This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor.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.

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.

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.

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.

Transplantation of human adipose-derived stem cells overexpressing LIF/IFN-ß promotes recovery in experimental autoimmune encephalomyelitis (EAE).

Multiple Sclerosis (MS) is the most common demyelinating disease with inflammatory demyelination in the central nerve system. Besides the defect in the myelin repair process, the balance change in inflammatory and anti- inflammatory cytokines is one of the most significant factors in MS pathogenesis. This study aimed at evaluating the effects of co-overexpressing beta interferon (IFN-ß) and Leukemia inhibitory factor (LIF) in human adipose-derived stem cells (IFN-ß/LIF-hADSCs) on the experimental autoimmune encephalomyelitis (EAE). 12 days after the induction of EAE on female mice C57Bl/6 with MOG35-55 and the emergence of primary clinical signs, the IFN-ß/LIF-hADSCs were injected into the mice tail vein of the EAE mice. The mice were sacrificed after 32 days and the spinal cords of the experimental groups were dissected out for the histopathologic and real-time RT-PCR studies. Here, we showed that the clinical scores and infiltration of mononuclear cells of treated mice with IFN-ß/LIF-hADSCs were decreased significantly. Demyelination and the number of Olig2+ and MBP+ cells were significantly increased in the test (IFN-ß/LIF-hADSCs) group. The findings revealed that the pattern of inflammatory and anti- inflammatory cytokines gene expression in the IFN-ß/LIF-hADSCs group was reversed compared to the control group. Overexpression of LIF as a neurotrophic and IFN-ß as an anti-inflammatory cytokine in hADSCs increases the immunomodulatory effect of hADSCs reduces the extent of demyelination, improves the number of Olig2+ cells, and also increases the amount of MBP protein which can increase the production of myelin in EAE model. This, besides hADSCs capacity for proliferation and differentiation, might enhance the treatment efficacy and provide a promising candidate for stem cell-based gene therapy of MS therapy in the future.

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.

Therapeutic effects of human adipose mesenchymal stem cells and their paracrine agents on sodium iodate induced retinal degeneration in rats.

AIMS: The degeneration of retinal neurons which occurs in many neurodegenerative diseases of retina such as retinitis pigmentosa and aged-related macular degeneration, is a progressive phenomenon and leads to permanent visual disability. Aside from their economic and social impact, those who suffer from these diseases have a poor quality of life due to the lack of cures. Researchers have turned to stem cell therapies as a potential solution to this global health crisis. Mesenchymal stem cells (MSCs) and their paracrine agents such as conditioned medium (CM) and exosomes (Exo) have been applied to treat different retinal disorders. This study compared the therapeutic effects of human adipose mesenchymal stem cells (hADSCs) and their secretome on an in vivo model of sodium iodate retinal neurodegeneration. MAIN METHODS: We analyzed the expression of retinal cells' specific mRNAs by RT-PCR and proteins by immunostaining as well as performing visual cliff avoidance test as a functional evaluation technique. There were four therapeutic groups in this study: hADSC, hADSC-CM, hADSC-Exo and hADSC-Exo + CM. KEY FINDINGS: Although all groups showed different therapeutic effects on various retinal cells, the results of hADSC-CM were most striking, especially in terms of photoreceptor regeneration and retinal function. SIGNIFICANCE: The findings of present study demonstrated the different effects of MSC-based therapies on various retinal cells which could be helpful in designing more precise treatments that suit to each neurodegenerative disease mechanism and the cells involved. It also suggests that CM might be a better choice due to its multifactorial characteristic.

Fournier's gangrene after missed acute perforated appendicitis: A case report.

Fournier's gangrene (FG) is a rare progressive necrotizing fasciitis (NF) with high mortality rate. This case report describes a young patient with FG with no known history of disease or invasive therapeutic interventions.

Therapeutic effects of mesenchymal stem cells-derived extracellular vesicles' miRNAs on retinal regeneration: a review.

Extracellular vesicles (EVs), which consist of microvesicles and exosomes, are secreted from all cells to transform vital information in the form of lipids, proteins, mRNAs and small RNAs such as microRNAs (miRNAs). Many studies demonstrated that EVs' miRNAs have effects on target cells. Numerous people suffer from the blindness caused by retinal degenerations. The death of retinal neurons is irreversible and creates permanent damage to the retina. In the absence of acceptable cures for retinal degenerative diseases, stem cells and their paracrine agents including EVs have become a promising therapeutic approach. Several studies showed that the therapeutic effects of stem cells are due to the miRNAs of their EVs. Considering the effects of microRNAs in retinal cells development and function and studies which provide the possible roles of mesenchymal stem cells-derived EVs miRNA content on retinal diseases, we focused on the similarities between these two groups of miRNAs that could be helpful for promoting new therapeutic techniques for retinal degenerative diseases.

In vitro Studies of Polycaprolactone Nanofibrous Scaffolds Containing Novel Gehlenite Nanoparticles.

BACKGROUND: Recently, many studies have been done on the physicochemical properties and biocompatibility of polycaprolactone (PCL) scaffolds containing ceramic reinforcers in the field of bone tissue engineering. In this study, the physical, mechanical and biological properties of electrospined-fabricated PCL scaffolds containing gehlenite (GLN) nanoparticles (NPs) as a novel bioceramic were investigated. METHODS: To obtain the appropriate mechanical properties, the solution contains 3%, 5%, 7%, and 10% wt. of GLN NPs were prepared. Fiber morphology was investigated by scanning electron microscopy. In order to evaluate the NPs distribution, Energy Dispersive X-Ray Spectroscopy, X-ray diffraction, and Fourier Transform Infrared Spectroscopy spectroscopy were used. The scaffold hydrophilicity was measured by the water contact angle test. The tensile test was used to check the mechanical strength of the scaffold. The proliferation of MG-63 cells was evaluated by the MTT test. Alkaline phosphatase (ALP) activity of MG-63 cells was also examined. RESULTS: Average fibers' diameters and porosity of PCL/GLN7% were obtained 150-500 nm and 80%, respectively. An increase in the scaffold hydrophilicity was observed by the addition of GLN NPs. The strength of PCL/GLN7% was higher than the blank PCL scaffold. Cell proliferation of scaffolds containing GLN was higher than the blank PCL scaffold. A significant increase in the secretion of ALP for GLN-loaded scaffolds was seen. DISCUSSION: The results showed that PCL/GLN7% composite scaffold could be a good candidate for bone tissue engineering. CONCLUSION: The overall results indicate that the scaffold (PCL /GLN7%) has suitable mechanical properties, a great cell compatibility for bone tissue regeneration.

Evaluation of Edaravone effects on the differentiation of human adipose derived stem cells into oligodendrocyte cells in multiple sclerosis disease in rats.

AIMS: Among all the treatments for Multiple Sclerosis, stem cell transplantation, such as ADSCs, has attracted a great deal of scientific attention. On the other hand, Edaravone, as an antioxidant component, in combination with stem cells, could increase the survival and differentiation potential of stem cells. MAIN METHODS: 42 rats were divided into: Control, Cuprizone (CPZ), Sham, Edaravone (Ed), hADSCs, and Ed/hADSCs groups. Following induction of cuprizone, induced MS model, behavioral tests were designed to evaluate motor function during. Luxal fast blue staining was done to measure the level of demyelination and remyelination. Immunofluorescent staining was used to evaluate the amount of MBP, OLIG2, and MOG proteins. The mRNA levels of human MBP, MOG, and OLIG2 and rat Mbp, Mog, and Olig2 were determined via RT-PCR. KEY FINDINGS: Flow cytometry analysis exhibited that the extracted cells were positive for CD73 (93.8 ± 3%) and CD105 (91.6 ± 3%), yet negative for CD45 (2.06 ± 0.5%). Behavioral tests, unveiled a significant improvement in the Ed (P < 0.001), hADSCs (P < 0.001), and Ed/hADSCs (P < 0.001) groups compared to the others. In the Ed/hADSCs group, the myelin density was significantly higher than that in the Ed treated and hADSCs treated groups (P < 0.01). Edaravone and hADSCs increased the expression of Mbp, Mog, and Olig2 genes in the cuprizone rat models. Moreover, significant differences were seen between the Ed treated and hADSCs treated groups and the Ed/hADSCs group (P < 0.05 for Mbp and Olig2 and P < 0.01 for Mog). SIGNIFICANCE: Edaravone in combination with hADSCs reduced demyelination and increased oligodendrogenesis in the cuprizone rat models.

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.

The Effect of Kiwifruit Therapeutics in the Treatment of Diabetic Foot Ulcer.

Diabetes mellitus is considered a silent disease with possible late chronic complications such as diabetic foot ulcer. This condition is managed by surgical debridement. To improve surgical outcome, some surgeons use proteolytic agents after surgery. Kiwifruit contains a type of proteolytic enzyme called actinidin that may play a role in the treatment of such complication. In the current study, we evaluate the role of kiwifruit extract in the treatment of diabetic foot ulcer. Eighteen diabetic foot ulcer patients were included in a randomized, double-blind clinical trial. The patients were divided randomly to control and experimental groups. Patients in the control group underwent daily wound dressing using base ointment (Eucerin). In the experimental group, we added kiwifruit extract to the standard wound dressing. Clinical data including general appearance of wound (according to recorded photographs before and after medical intervention) were analyzed using SPSS version 22. The mean wound area of the experimental group was significantly less than in the control group (P = .005) after 4 weeks of treatment. Comparison of the average of size difference, before and after the treatment in the experimental group and the control group, shows that kiwifruit can have a good impact on wound healing (P = .0001). In patients with diabetic foot ulcer, wound dressing using kiwifruit extract may help reduce time of treatment and may replace surgical debridement for some selected cases.

Chondrogenic activity of two herbal products; pomegranate fruit extract and avocado/soybean unsaponifiable.

BACKGROUND AND PURPOSE: Articular cartilage defects aren't repaired by itself. Numerous studies have been conducted in the area of cartilage tissue engineering and some of them considered herbal products. An attempt was made in this study to compare the effects of pomegranate fruit extract (PFE), avocado/soybean unsaponifiable (ASU), and their equal proportional mixture on the chondrogenesis of human adipose-derived stem cells (hADSCs). EXPERIMENTAL APPROACH: PFE was prepared through the percolation method. ASU powder was dissolved in ethanol at 10 µg/mL concentration and was sterilized. The hADSCs first were isolated, expanded in monolayer culture and identified, and next seeded on fibrin scaffolds. The hADSCs/fibrin scaffolds were divided into 4 groups of control, ASU, PFE, and PFE+ ASU and subjected to in vitro induction for 2 weeks. The control group received chondrogenic medium, other groups received chondrogenic medium plus ASU, PFE, or PFE + ASU, respectively. The MTT assay was performed for cell viability evaluation, real-time polymerase chain reaction for expression of cartilage genes, and the toluidine blue, safranin-O, and immunohistochemistry for staining of the constructs. FINDINGS / RESULTS: Cell viability, cartilage genes expression, matrix staining density, and collagen II protein levels in PFE samples were significantly higher than those of the other groups (P < 0.05). Histological assessments revealed more chondrogenic centers (P < 0.05) in the PFE group compared to the other groups. CONCLUSION AND IMPLICATIONS: In this study, it was revealed that PFE can be considered as an induction factor for future chondrogenic studies.

Assessment of ability of human adipose derived stem cells for long term overexpression of IL-11 and IL-13 as therapeutic cytokines.

Adipose-derived stem cells (ADSCs) are a type of mesenchymal stem cells with the therapeutic effects that make them one of the best sources for cell therapy. In this study, we aimed to assess the ability of human ADSCs for constant expression of IL-11 and IL-13, simultaneously. In this study, the characterized hADSCs were transduced with a lentiviral vector (PCDH-513B) containing IL-11 and IL-13 genes, and the ability of long-term expression of the transgenes was evaluated by ELISA technique on days 15, 45 and 75 after transduction. Our results indicated a high rate of transduction (more than 90%) in the isolated hADSCs. Our data showed the highest rate of expression on days 75 after transduction which was 242.67 pg/ml for IL-11 and 303.6 pg/ml for IL-13 compared with 35.2 pg/ml and 35.6 pg/ml in untreated cells, respectively (p = 0.001). Besides, MTT assay showed transduction of hADSCs with lentiviral viruses containing IL-11 and IL-13 had no adverse effect on hADSCs proliferation (p-value = 0.89). Finally, we successfully constructed a hADSC population stably overexpressing IL-11 as the neurotrophic cytokine and IL-13 as the anti-inflammatory cytokine and this transduced cells can be used for further studies in EAE mice model.

The immunoregulatory and neuroprotective effects of human adipose derived stem cells overexpressing IL-11 and IL-13 in the experimental autoimmune encephalomyelitis mice.

Multiple sclerosis (MS) is an inflammatory demyelination disease in the central nervous system (CNS) characterized by incomplete endogenous remyelination in the chronic phase. A shift of the balance between pro and anti-inflammatory cytokines is one of the important markers in the pathogenesis of MS. This study aimed to evaluate the effects of human adipose derived stem cells (hADSCs) overexpressing interleukin 11 and interleukin 13 (IL-11, 13-hADSCs) on the experimental autoimmune encephalomyelitis (EAE), an animal model of MS.12 days after immunization of C57Bl/6 female mice with MOG35-55 and initial clinical symptoms appearance, the IL-11, 13-hADSCs were injected via the tail vein into the EAE mice. Then, the mice were sacrificed at 30 days post-immunization (DPI) and the spinal cords of experimental groups were extracted for histopathological and real-time RT-PCR studies.The results indicated that the clinical scores and mononuclear cells infiltration into the spinal cords of EAE mice were significantly reduced in mice treated with IL-11, 13-hADSCs. Likewise, the remyelination and oligodendrogenesis were significantly enhanced in the mentioned treatment group. Real-time results demonstrated that pro/anti-inflammatory cytokine genes expression was reversed in IL-11, 13-hADSCs treatment group in comparison to the untreated EAE group.Expression of IL-11 as a neurotrophic cytokine and IL-13 as an anti-inflammatory cytokine by hADSCs could increase the immunomodulatory and neuroprotective effects of hADSCs and be a powerful candidate in stem cell therapy for future treatment of MS.