Resveratrol-coated chitosan mats promote angiogenesis for enhanced wound healing in animal model.

BACKGROUND: Growing incidences of chronic wounds recommend the development of optimal therapeutic wound dressings. Electrospun nanofibers have been considered to show potential wound healing properties when accompanied by other wound dressing materials. This study aimed to explore the potential role of Chitosan (CS) nanofibrous mats coated with resveratrol (RS) as an antioxidant and pro-angiogenic agent in rat models of skin wound healing. METHODS: Electrospun chitosan/polyethylene oxide (PEO) nanofibers were prepared using electrospinning technology and coated by 0.05 and 0.1 mg.ml resveratrol named as (CS/RS 0.05) and (CS/RS 0.1), respectively. The scaffolds were characterized physiochemically such as in vitro release study, TGA, FTIR spectroscopy analysis, biodegradability, and human dermal fibroblast seeding assay. The scaffold was subsequently used in vivo as a skin substitute on a rat skin wound model. RESULTS: In vitro tests revealed that all scaffolds promoted cell adhesion and proliferation. However, more cell viability was observed in CS/RS 0.1 scaffold. The biocompatibility of the scaffolds was validated by MTT assay, and the results did not show any toxic effects on human dermal fibroblasts. It was observed that RS-coated scaffolds had the ability to release RS in a controlled manner. In in vivo tests CS/RS 0.1 scaffold had the greatest impact on the healing process by improving the neodermis formation and modulated inflammation in wound granulation tissue. Histological analysis revealed enhanced vascular endothelial growth factor expression, epithelialization and increased depth of wound granulation tissue. CONCLUSIONS: The RS-coated CS/PEO nanofibrous scaffold accelerates wound healing and may be useful as a dressing for cell transfer and clinical skin regeneration.

Autophagy enhances the differentiation of insulin-producing cells from Wharton's jelly-derived mesenchymal stem cells.

Autophagy disruption suppresses insulin production and induces diabetes. The role of autophagy in the differentiation of Wharton's jelly (WJ)-derived mesenchymal stem cells (WJSCs) into insulin-producing cells (IPCs) was investigated in this experimental study. The WJSCs were incubated in a differentiation medium (DM) with or without an autophagy inhibitor (3-methyladenine: 3MA). The differentiation of IPCs was confirmed by flow cytometry analysis of PDX-1 and insulin-positive cells, insulin secretion, and the high expression of ß cell-specific genes, Glucose transporter 2 (GLUT-2), and INSULIN. Autophagy has been assessed by calculating the percentage of Acridine orange (AO)-positive cells, expression of autophagy-related genes, and the LC3B/LC3A ratio. ß cell-specific genes were up-regulated in the DM group, and 3MA decreased their expression. In the DM+3MA-treated cells, the expression of GLUT-2 and INSULIN genes and insulin secretion decreased compared to the DM group. In cells treated with 3MA, there was a significant decrease in the percentage of PDX-1 and insulin-positive cells compared to 3MA-untreated cells. Additionally, in the group receiving both DM and 3MA treatment, the expression of autophagy-related genes, the LC3B/LC3A protein ratio, and the percentage of AO-stained cells were significantly reduced compared to the group receiving only DM treatment. These findings suggest autophagy is essential for ß cell differentiation and insulin secretion.

Dose-dependent renoprotective effect of vanillic acid on methotrexate-induced nephrotoxicity via its anti-apoptosis, antioxidant, and anti-inflammatory properties.

Methotrexate-induced nephrotoxicity is a medical emergency which is associated with a variety of side effects. Vanillic acid (VA), as an antioxidant, removes free radical oxygen to protect cell defense. Therefore, this study investigated VA's beneficial effects on nephrotoxicity induced by methotrexate through its anti-apoptosis, antioxidant, and anti-inflammatory properties. Our study included five groups of male Wistar rats (n = 8): sham, MTX (Methotrexate) group: rats receiving methotrexate (20 mg/kg, intraperitoneally) on Day 2. Moreover, the remaining groups consisted of animals that received vanillic acid (25, 50, and 100 mg/kg, orally for seven days) plus MTX on the 2nd day. The rats were deeply anesthetized on the eighth day to obtain blood and renal tissue samples. The results showed that MTX can increase blood urea nitrogen and creatinine. However, VA (50 and 100 mg/kg) improved renal function as approved by histological findings. Compared with MTX-treated rats, VA enhanced the contents of total antioxidant capacity (TAC) and reduced renal malondialdehyde (MDA). Moreover, VA reduced mRNA expressions of caspase-3 and Bcl-2-associated x protein (Bax) and caused mRNA overexpression of the renal B-cell lymphoma-2 (Bcl-2), and Nrf-2 (Nuclear factor erythroid 2-related factor 2) compared to the MTX group. Also, VA administration significantly reduced inflammatory agents. Overall, VA protects the kidneys against methotrexate-induced nephrotoxicity via anti-apoptosis, antioxidant, and anti-inflammatory properties. Our results revealed that the most effective dose of VA was 100 mg/kg.

A high-efficient antibacterial and biocompatible polyurethane film with Ag@rGO nanostructures prepared by microwave-assisted method: Physicochemical and dermal wound healing evaluation.

Wound infections are a significant issue that can hinder the wound healing process. One way to address this problem is by enhancing the antibacterial activity of wound dressings. Accordingly, this work focuses on developing a castor-oil-based antibacterial polyurethane nanocomposite film impregnated with silver nanoparticles (AgNPs) decorated on the surface of reduced graphene oxide (rGO) nanostructures (Ag@rGO). To this aim, rGOs act as a platform to stabilize AgNPs and improve their bioavailability and dispersion quality within the PU film. The microwave-assisted synthesis of Ag@rGO nanohybrids was proved by FTIR, XRD, TGA, FE-SEM, EDS, and TEM analyses. Compared to PU/GO, the effect of Ag@rGO nanohybrids on thermo-mechanical features, morphology, antibacterial activity, cytocompatibility, and in vivo wound healing was assessed. SEM photomicrographs revealed the enhanced dispersion of Ag@rGO nanohybrids compared to GO nanosheets. Besides, according to XRD results, PU/Ag@rGO nanocomposite film demonstrated higher microphase mixing, which could be due to the finely dispersed Ag@rGO nanostructures interrupting the hydrogen bonding interactions in the hard segments. Moreover, PU/Ag@rGO nanocomposite showed excellent antibacterial behavior with completely killing E. coli and S. aureus bacteria. In vitro and in vivo wound healing studies displayed PU/Ag@rGO film effectively stimulated fibroblast cells proliferation, migration and re-epithelialization. However, the prepared antibacterial PU/Ag@rGO nanocomposite film has the potential to be used as a biomaterial for dermal wound healing applications.

Bioactive chitosan/poly(ethyleneoxide)/CuFe2O4 nanofibers for potential wound healing.

Wound healing is a complex process that often requires intervention to accelerate tissue regeneration and prevent complications. The goal of this research was to assess the potential of bioactive chitosan@poly (ethylene oxide)@CuFe2O4 (CS@PEO@CF) nanofibers for wound healing applications by evaluating their morphology, mechanical properties, and magnetic behavior. Additionally, in vitro and in vivo studies were conducted to investigate their effectiveness in promoting wound healing treatment. The nanoparticles exhibited remarkable antibacterial and antioxidant properties. In the nanofibrous mats, the optimal concentration of CuFe2O4 was determined to be 0.1% Wt/V. Importantly, this concentration did not adversely affect the viability of fibroblast cells, which also identified the ideal concentration. The scaffold's hemocompatibility revealed nonhemolytic properties. Additionally, a wound-healing experiment demonstrated significant migration and growth of fibroblast cells at the edge of the wound. These nanofibrous mats are applied to treat rats with full-thickness excisional wounds. Histopathological analysis of these wounds showed enhanced wound healing ability, as well as regeneration of sebaceous glands and hair follicles within the skin. Overall, the developed wound dressing comprises CuFe2O4 nanoparticles incorporated into CS/PEO nanofibrous mats demonstrating its potential for successful application in wound treatment.

Prenatal exposure to crude oil vapor reduces differentiation potential of rat fetal mesenchymal stem cells by regulating ERK1/2 and PI3K signaling pathways: Protective effect of quercetin.

It has been indicated that crude oil vapor (COV) induces tissue damage by several molecular mechanisms. Quercetin (QT) as an important component of food with antioxidant properties has a protective role against cell toxicity caused by many pollutants. However, data related to the adverse effects of crude oil vapor (COV) on stem cell fate and differentiation and the role of quercetin (QT) in protecting stem cells against the toxicity caused by these pollutants is very limited. This study aimed to explore the protective effect of QT against the adverse effects of COV on fetal mesenchymal stem cells (fMSCs) differentiation. Twenty-four pregnant Wistar rats were categorized into 4 groups including the control, COV, COV+QT, and QT. Rats were exposed to COV from gestational day (GD) 0-15 and received QT by gavage. The fMSCs were isolated from fetuses, and cell proliferation, differentiation potential, expression of osteogenesis and adipogenesis-related genes, and phosphorylation of PI3K and ERK1/2 signaling proteins were evaluated. The results showed that COV reduced the proliferation and differentiation of fMSCs through the activation of PI3K and ERK1/2 signaling pathways. Also, COV significantly decreased the expression of osteonectin, ALP, BMP-6, Runx-2, PPARγ, and CREBBP genes in differentiated cells. QT treatment increased the proliferation and differentiation of fMSCs in COV-exposed rats. In conclusion, our findings suggest that prenatal exposure to COV impaired fMSCs differentiation and QT reduced the adverse effects of COV by regulating ERK1/2 and PI3K signaling pathways.

The renoprotective effects of hesperidin on kidney injury induced by exposure to severe chronic dust storm particulate matter through inhibiting the Smads/TGF-ß1 signaling in rat.

Exposure to dust storm particulate matter (PM) is detrimental to kidney tissue. In this study, the impacts of chronic intake of dusty PM were explored as a major objective in a specified compartment to make a real-like dust storm (DS) model, and the role of hesperidin (HSP) as an antioxidant on kidney tissue was assessed in rats. Thirty-two male Wistar rats (200-220 g) were randomly allocated into 4 groups: CA+NS: (clean air and normal saline as a vehicle of HSP). Dusty PM and NS (DS+NS). HSP+ CA: rats received 200 mg/kg of HSP by gavage for 28 days, once daily in addition to exposure to clean air. HSP+DS: HSP plus DS. In DS groups, the animals were exposed to dust storms at a concentration of 5000-8000 µg/m3 in the chamber for 1 h daily, for 4 consecutive weeks, except Thursdays and Fridays. At the end of the experiment, the animals were sacrificed for biochemical, inflammatory, oxidative stress, molecular parameters, and histological evaluation. DS significantly enhanced blood urea nitrogen and creatinine, inflammatory (tumor necrosis factor-α, and interleukin-1ß), and oxidative stress indexes. Likewise, a significant increase was seen in mRNA Smads, collagen-I, and transforming growth factor-ß1 (TGF-ß1) expressions in the kidney. Histological findings showed contracted glomeruli and kidney structure disorder. In addition, Masson's trichrome staining demonstrated renal fibrosis. Nevertheless, HSP could significantly reverse these changes. Our data confirmed that DS results in kidney fibrosis through enhancing Smads/TGF-ß1 signaling. However, HSP was able to inhibit these changes as confirmed by histological findings.

Evaluation of the effects of ethanol and mitomycin on survival of rat limbal stem cells: an in vitro study.

PURPOSE: Ethanol and mitomycin C (MMC) are clinically used to treat corneal diseases such as LASEK and LASIK surgery. In this study, we investigated the effects of time-dependent alcohol and MMC in cultured rat limbal stem cells (LSCs) to determine the appropriate time for the use of this compound in the clinical setting. METHODS: LSCs (N = 10 eyes) isolated from male Wistar rats were cultured and characterized; then, isolates were divided into three groups. One group was exposed to a 20% concentration of ethanol for 5, 10, 15, 20, 25, and 30 s, and cell viability was assessed one, three, and five days following ethanol exposure using an MTT assay. To investigate the effect of MMC, cells in the second group were treated with 0.02% MMC in various periods (i.e., 15 s, 30 s, 60 s, 90 s, and 120 s) and time-dependent responses of cultured LSCs were recorded. Cells in the third group were co-treated with ethanol and MMC; then, dose and time dependency was evaluated. RESULTS: In comparison with the viable cells in the control group, ethanol markedly decreased the viability of cells in a time-dependent manner in days one and three. On day five, the viability of LSCs was improved significantly (p < 0.05) in comparison with day one. The number of viable progenitor cells was significantly decreased after MMC treatment in a time-dependent manner, as determined by the MTT assay (p < 0.001). The use of mitomycin, along with alcohol, decreased cell viability in all groups treated with ethanol + MMC compared to the control on days one, three, and five (p < 0.0001). CONCLUSIONS: Our findings suggest that ethanol and MMC reduced cell viability in cultured LSCs in a time-dependent manner. In addition, when LSCs were exposed to alcohol alone, they had a better recovery process within 5 days in comparison to when exposed to mitomycin alone or mitomycin + alcohol.

Antibacterial and antioxidant double-layered nanofibrous mat promotes wound healing in diabetic rats.

Diabetic wounds are problematic to heal owing to microbial infections as well as decreased proliferation and high concentrations of reactive oxygen species. In this study, a double-layered nanofibrous mat containing grape seed extract (GSE) and silver sulfadiazine (SSD) was fabricated. A synthetic biodegradable polymer, e.g., polycaprolactone (PCL), and a natural material (i.e., collagen) were employed as wound dressing substances. The results showed that GSE possesses antioxidant activity which can be helpful in reducing free radicals. The platform exhibited antibacterial activity against gram-positive and -negative bacteria. The double-layered nanofibrous mat containing GSE and SSD not only was not toxic but also amplified the cell proliferation compared to a pure mat, showing the effect of plant extract. After induction of a round wound, the animals were divided into three groups, namely (1) normal group (receiving + GSE/-GSE nanofiber), (2) diabetic group (receiving + GSE/-GSE nanofiber), and (3) control group (receiving gauze). In vivo evaluation demonstrated no significant differences in the healing process of normal rats. Surprisingly, fully repaired skin was observed on day 14 in the double-layered nanofibrous mat containing GSE in the normal and diabetic groups whereas the wound of diabetic rats treated with pure mat was not completely healed. The macroscopic and microscopic results after 14 days showed the following order in wound repair: Normal/ + GES > Diabetic/ + GSE > Normal/-GES > Diabetic/-GSE > control (with gauze) (p < 0.05). Accordingly, the double-layered nanofibrous mat containing GSE and SSD used in the present study could be considered as a suitable wound dressing in order to shorten healing time and prevent infection during the wound healing process.

Adipose-derived mesenchymal stem cells in emphysema: Comparison of inflammatory markers changes in response to intratracheal and systemic delivery method.

Cytokines are the most important inflammatory mediators and are well-known as the main cause of emphysema. Adipose-derived stem cells (ADSCs) as a cell-based treatment strategy could play a pivotal role in lung regeneration through anti-inflammatory and paracrine properties. Accordingly, the aim of this study was to the comparison of inflammation markers' improvement in response to the intratracheal and systemic delivery method of adipose-derived mesenchymal stem cells in emphysema. Forty-eight rats were divided into five groups including Control, Elastase (25 IU/kg, Intratracheal, at day first and 10th), Elastase+PBS, Intratracheal cell therapy (1 ×107, at day 28th), and Systemic cell therapy groups (1 ×107, Jugular vein, at day 28th). After 3 weeks, the blood gas analysis (PO2, PCO2 and pH), fibrinogen level, and C-reactive protein (CRP) concentrations were measured in all groups. In addition, inflammatory genes expression, and concentration levels of pro and anti-inflammatory cytokines (IL-6, IL-17, TNF-α, and TGF-ß,) were evaluated using Real-time PCR and Elisa kits, respectively. The statistical analysis of our data shows that local administration leads to more significant treatment efficacy with decreased inflammation parameters such as WBC count and pro-inflammatory cytokines in comparison with systemic treatment. Besides, these results were approved by more reduction of CRP and fibrinogen concentration levels in blood samples of intra-tracheal AMSCs-treated rats compare with the systemic group. Moreover, the improvement in histopathology indexes of the local administrated group was significantly better than the systemic group. Accordingly, the obtained results suggest local administration as the most efficacious route for mesenchymal stem cells delivery in patients with emphysema.

Evaluation of effects of riboflavin and/or ultraviolet-A on survival of rat limbal epithelial stem cells in ex-vivo.

Purpose: To investigate the effects of riboflavin and/or ultraviolet-A (UV-A) irradiation on the cell viability of ex-vivo-cultured rat limbal stem cells (LSCs). Methods: LSCs of male Wistar rats (N = 12 eyes) were cultured, and immunofluorescence staining was performed to evaluate them. After characterization, these cells were assigned to four groups of control (C), a group that was exposed to UV-A radiation (UV), a group that was treated with riboflavin (R), and a group that cotreated with both UV-A and riboflavin (UV+R). To determine the cell viability of LSCs, these cells were subjected to MTT assay on days 1, 3, and 7 after exposure to UV-A and/or riboflavin. The duration of exposure to UV-A and riboflavin was similar to levels used during the conventional corneal collagen cross-linking procedure. Results: Compared with the viable cells in the control group, there was a significant decrease (P < 0.0001) in the number of LSCs in the UV group during all study days. In the R group, the level of viable LSCs was as same as the level of viable LSCs in the C group. Combined treatment with UV-A plus riboflavin significantly decreased the survival of LSCs on days 1 and 3 (P < 0.0001, P < 0.001, respectively) compared with the control group. Interestingly, in the UV+R group, the photosensitizing effect of riboflavin significantly decreased the cytotoxic effect of UV irradiation 7 days after exposure. Conclusion: These results suggest that the administered UV energy in the presence or absence of riboflavin can damage LSCs. Likewise, riboflavin could decrease the toxic effect of UVA on LSCs.

Antibacterial Host-Guest Intercalated LDH-Adorned Polyurethane for Accelerated Dermal Wound Healing.

Curcumin has a limited clinical application because of its extremely poor accessibility. In the present study, improved curcumin bioavailability within a castor oil polyurethane/layered double hydroxide (LDH) wound cover was achieved by preparing a curcumin p-sulfonic acid calix[4]arene (SC4A) inclusion complex. Then, it was utilized to intercalate MgAl-layered double hydroxide (MgAl-LDH) nanosheets. The incorporation of the nanostructure into a PU/Cur-SC4A-LDH film provided bacteria-killing performance against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria. This finding is due to an increase in curcumin bioavailability in the PU matrix. Furthermore, all PU nanocomposites exhibited appropriate cytocompatibility based on an MTT assay. Mainly, the proliferation of L929 fibroblast cells in contact with the PU/Cur-SC4A-LDH sample was significantly further enhanced than that for other nanocomposites within 7 days. This observation can be related to the better availability of curcumin on the film's surface, which causes an improvement in the proliferation rate of cells. Regarding the histological results, the hematoxylin and eosin (H&E) images showed faster epidermal layer formation and a larger quantity of matured hair follicles for PU/Cur-SC4A-LDH-healed wounds in comparison with those for the negative control over a period of 28 days. Thus, this practical healing ability of the PU/Cur-SC4A-LDH nanocomposite makes it a promising candidate as a wound dressing film.

Spleen extracellular matrix provides a supportive microenvironment for ß-cell function.

Objectives: Type 1 diabetes mellitus is a common autoimmune and multifactorial disorder. Researchers have been interested in making a favorable islet-like tissue model for the treatment of diabetes. The main objective of this study was to determine the effects of the spleen extracellular matrix (S-ECM) on the function of the MIN6 cell line (a ß-cell model). Materials and Methods: In this experimental research, Wistar rat spleens were decellularized by sodium dodecyl sulfate (SDS) and Triton X-100. S-ECM was characterized by histological assessments, scanning electron microscopy, determination of residua DNA, and examination of the mechanical tensile property. Then, MIN6 cells were seeded on S-ECM scaffold. Glucose-stimulated insulin secretion and mRNA expression of insulin-related genes were examined to confirm the function of the cells. Results: The main components of S-ECM such as collagen and glycosaminoglycan remained after decellularization. Furthermore, very low residual DNA and appropriate mechanical behavior of S-ECM provided an ideal extracellular microenvironment for the MIN6 cells. GSIS results showed that the seeded cells in S-ECM secreted more insulin than the traditional two-dimensional (2D) culture. The expression of specific insulin-related genes such as PDX-1, insulin, Maf-A, and Glut-2 in the recellularized scaffold was more significant than in the 2D traditional cultured cells. Also, MTT assay results showed that S-ECM were no cytotoxic effects on the MIN6 cells. Conclusion: These results collectively have evidenced that S-ECM is a suitable scaffold for stabilizing artificial pancreatic islands.

Decellularized Wharton's jelly scaffold enhances differentiation of mesenchymal stem cells to insulin-secreting cells.

Diabetes is caused by the destruction of beta-cells in the pancreatic islets. This study was designed to fabricate a favorable bio-scaffold to improve the differentiation of Wharton's jelly (WJ) mesenchymal stem cells (WMJSCs) to the insulin-secreted cells (ISCs). In this study, a decellularized-WJ scaffold (DWJS) was established and characterized by histological assessments, scanning electron microscopy, determination of residual DNA, and examination of the mechanical tensile property. The WJMSCs were seeded on DWJS and exposed to ISC-differentiation media. The functional maturity of ISCs was examined using Ditizone (DTZ) staining, insulin and C-Peptide secretion, and mRNA expression of insulin-related genes. The main components of the WJ such as collagens, proteoglycans, and glycosaminoglycans remained after decellularization. Very low residual DNA, good mechanical behavior, and appropriate porosity of the DWJS provided an ideal extracellular microenvironment for the ISCs. The insulin secretion of DWJS-seeded ISCs in response to glucose stimulation was significantly more than that in the 2D-culture system. DWJS significantly increased the number of DTZ-positive cells compared to the 2D-culture system. In addition, it enhanced the expression of the PDX-1, GLUT-2, and INS genes in the ISCs. These results collectively provided solid evidence that DWJS is a suitable scaffold for stabilizing the artificial pancreatic island.

Gallic Acid Improves Therapeutic Effects of Mesenchymal Stem Cells Derived from Adipose Tissue in Acute Renal Injury Following Rhabdomyolysis Induced by Glycerol.

Acute kidney injury (AKI) is identified by a progressive reduction in the glomerular filtration rate (GFR) and retention of nitrogenous waste products. Traumatic and nontraumatic rhabdomyolysis is recently considered the main cause of AKI. According to several studies, stem cell treatment is a promising therapeutic strategy for many types of disorders including AKI. The main limitation of mesenchymal stem cells (MSCs) therapy is reducing cell survival in response to oxidative stress products in injured organ areas. Gallic acid (GA) as a well-known antioxidant has been reported to confer potent-free radical scavenging and anti-inflammatory properties. Therefore, the aim of the current study was to assess the influence of MSCs and GA in acute renal injury following rhabdomyolysis induced by glycerol. A total of 70 healthy rats were divided into seven groups (10 in each group): control, AKI (glycerol, intramuscular), cell therapy (AKI + intravenous injection of mesenchymal stem cells derived from adipose tissue (AMCs), AKI + AMCs + GA (50, 100, and 200 mg/kg, intraperitoneally, 3 days a week for 3 consecutive weeks), and positive control group (the most effective dose of gallic acid). After the treatment, rats were sacrificed; blood, urine, and kidney tissues were collected; and qualitative and quantitative parameters (including blood urea nitrogen (BUN), creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate transaminase (SGOT), oxidative stress markers kidney function parameters) and histopathological indexes were assayed. Our results revealed that co-treatment of AMCs plus GA into AKI rats decreased BUN and creatinine and ameliorated kidney injury parameters after 3 weeks. Improved oxidative stress markers such as decreased MDA and increased SOD and CAT were significant in the GA + AMCs group compared to the AMCs alone in AKI rats. Also, the histopathological appearances of AKI rats including renal tubule cavity expansion and renal tubular epithelial cell edema, and interstitial inflammation, were alleviated using GA + AMCs treatment compared to the control. The obtained results of the current study documented that antioxidants could make mesenchymal stem cells more resistant to the condition in which they are supposed to be transplanted and probably improve the efficacy of stem cell therapy in AKI patients.

Stem cell-based and mesenchymal stem cell derivatives for coronavirus treatment.

Coronavirus disease 2019 (COVID-19) as one of the types of pneumonia was first reported in Wuhan, China in December 2019. COVID-19 is considered the third most common coronavirus among individuals after acute respiratory syndrome (SARS-CoV) and the Middle East respiratory syndrome (MERS-CoV) in the 20th century. Many studies have shown that cell therapy and regenerative medicine approaches have an impressive effect on different dangerous diseases in a way that using a cell-based experiment could be effective for improving humans with severe acute respiratory infections caused by the 2019 novel coronavirus. Accordingly, due to the stunning effects of mesenchymal stem cells (MSCs) and derivatives on the treatment of various diseases, this review focuses on the auxiliary role of MSCs and their derivatives in reducing the inflammatory processes of acute respiratory infections resulted from the 2019 novel coronavirus. The reported MSCs treatment outcomes are significant because these cells prevent the immune system from overactivating and improve, endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection. The MSCs can be an effective, autologous, and safe treatment, and therefore, share the results. To date, the results of several studies have shown that MSCs and their derivatives can inhibit inflammation. Exosomes act as intercellular communication devices between cells for the transfer of active molecules. In this review, recent MSCs and their derivatives-based clinical trials for the cure of COVID-19 are introduced.

Adipose-derived mesenchymal stem cells protects renal function in a rat model of emphysema.

BACKGROUND AND OBJECTIVE: The link between lung disease and kidney disorders has already been confirmed. Previous studies have documented that obstructive pulmonary disease is an independent predictor of decreased renal function, which reduces glomerular filtration rate. Recently, mesenchymal stem cells are the most important cell used in cell therapy. Accordingly, the present experiment was designed to evaluate the efficacy of adipose-derived mesenchymal stem cells (AMSCs) on improvement of renal function in elastase induced-pulmonary emphysema rats. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats divided into the 3 groups. Following intra-tracheal administration of elastase, the in vivo emphysema model established and confirmed according to the specific markers. Subsequently, systemic AMSCs injection was developed. the kidney injuries markers such as Blood urea nitrogen (BUN), creatinine, sodium and potassium as well as the kidney histopathologic parameters were assessed in all groups. Moreover, the oxidative stress markers levels including Malondialdehyde (MDA), Total antioxidant capacity (TAC), Catalase (CAT) and Glutathione peroxidase (GPx) were measured in kidney tissue and also inflammatory cytokines including IL-10, IL-6, and IFN-Ƴ were assessed in serum samples. RESULTS: The marked rise in kidney injuries markers were observed which showed by enhancement of BUN and Creatinine levels in emphysema rats compared to the control. Furthermore, the results demonstrated increases in MDA levels and decreases in antioxidant activity which was in line with increases in inflammation cytokines in renal tissue. Conversely, AMSCs treatment improved renal function as shown by the decreases BUN, Creatinine and proteinuria. Furthermore, renal histological assay demonstrate improvement in glomerular and tubular damage and inflammatory cells accumulation. CONCLUSIONS: Our results documented the promising kidney-protective properties of Adipose-Derived Mesenchymal Stem Cells in the kidney injuries induced by emphysema.

Incorporation of Silver Sulfadiazine into An Electrospun Composite of Polycaprolactone as An Antibacterial Scaffold for Wound Healing in Rats.

OBJECTIVE: Fabrication of an antibiotic-loaded scaffold with controlled release properties for wound dressing is one of tissue engineering challenges. The aim of this study was to evaluate the wound-healing effectiveness of 500-µm thick polycaprolactone (PCL) nanofibrous mat containing silver sulfadiazine (SSD) as an antibacterial agent. MATERIALS AND METHODS: In this experimental study, an electrospun membrane of PCL nanofibrous mat containing 0.3% weight SSD with 500 µm thickness, was prepared. Morphological and thermomechanical characteristics of nanofibers were evaluated. Drug content and drug release properties as well as the surface hydrophobicity of the nanofibrous membrane were determined. Antimicrobial properties and cellular viability of the scaffold were also examined. A full thickness wound of 400 mm2 was created in rats, to evaluate the wound-healing effects of PCL/SSD blend in comparison with PCL and vaseline gas used as the control group. RESULTS: SSD at a concentration of 0.3% improved physicochemical properties of PCL. This concentration of SSD did not inhibit the attachment of human dermal fibroblasts (HDFs) to nanofibers in vitro, but showed antibacterial activity against Gram-positive Staphylococcus aureus (ST) and Gram-negative Pseudomonas aeruginosa (PS). Overall, results showed that SSD improves characteristics of PCL nanofibrous film and improves wound-healing process in one-week earlier compared to control. CONCLUSION: Cytotoxicity of SSD in fabricated nanofibrous mat is a critical challenge in designing an effective wound dressing that neutralizes cellular toxicity and improves antimicrobial activity. The PCL/SSD nanofibrous membrane with 500- µm thickness and 0.3% (w/v) SSD showed applicable characteristics as a wound dressing and it accelerated wound healing process in vivo.

Isolating human dermal fibroblasts using serial explant culture.

BACKGROUND: The purpose of this study was to introduce an applicable culture technique to isolate human dermal fibroblasts (HDFs); which could also contribute to research, clinical practices, as well as tissue engineering. METHODS: Samples from the human skin were dissected and cultured via serial explant technique. Subsequently, the isolated fibroblasts were assessed for their protein markers and genetic variations via immunofluorescence (IF) and karyotyping; respectively. Following the employment of this technique, a small piece of explant completely disappeared; while no dermis remained after 10 days. RESULTS: The quantity of HDFs harvested through this culture technique was reported at a normal level. The results of immunostaining also indicated that the isolated fibroblasts had expressed vimentin and fibronectin; whereas no cells had shown cytokeratin and epidermal marker. Moreover, karyotyping results for the fibroblasts isolated by the given technique revealed no chromosomal diversity after passage 20. CONCLUSIONS: It was concluded that serial explant culture was an efficient technique for isolating HDFs from a small piece of skin in short-time periods; which could also preserve their normal morphology and molecular characteristics.

Protective effects of Curcumin on testicular toxicity induced by titanium dioxide nanoparticles in mice.

OBJECTIVE: In this study, we investigated the preventing effects of Curcumin (Cur) against titanium dioxide nanoparticle (NTiO2)-induced mouse testicular damage. METHODS: We assessed NTiO2-intoxicated mice received 50mg/kg of NTiO2 for 35 days. The Cur + NTiO2 group was pretreated with Cur (200 mg/kg) for 7 days prior to administering NTiO2. Sperm parameters, testosterone concentration, histological criteria, morphometric parameters and Johnsen's scoring. RESULTS: NTiO2 significantly reduced testicular weight, testosterone concentration, morphometric parameters, Johnsen's scoring and sperm quality (p<0.01), as well as a significant increase in histological criteria. Pretreatment with Cur reduced testicular weight, ameliorated morphometric parameters, increased Johnsen's scoring, elevated testosterone levels, and increased histological criteria such as vacuolization, detachment, and sloughing of germ cells into the seminiferous tubules. Cur also improved sperm parameters including sperm count, motility, and percentage of abnormality. CONCLUSION: Cur was found to have a potent protective effect against spermatogenesis defects induced by nanoparticles in mice.