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The aim of this research is to compare the capabilities of Adipose tissue mesenchymal stem cells (AT-MSCs) and bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of diabetic male mice with CLI model. Supernatants were collected from C57BL/6 mice isolated AT-MSCs and BM-MSCs, afterward their effects on human umbilical vein endothelial (HUVEC) migration potential were evaluated. Diabetes mellitus type 1 was induced by streptozotocin injection. Diabetic mice with CLI model were divided into three groups and injected with AT-MSCs, BM-MSCs, or PBS then the efficacy of them was assessed. Survival of MSCs was analysed by SRY-specific gene. The conditioned medium of AT-MSCs and BM-MSCs stimulated HUVECs migration and the donor cells were detected till 21 day in two groups. BM-MSCs and AT-MSCs improved significantly functional recovery and ischemia damage. Neovascularization in ischemic muscle was significantly higher in mice treated with AT-MSCs and BM-MSCs and they improved muscle regeneration. In vivo and in vitro findings show that AT-MSCs and BM-MSCs transplantation could be proposed as a promising therapy to promote angiogenesis and muscle regeneration through secretion of proangiogenic factors, cytokines and growth factors in diabetic mice with CLI model wherein blood supply is insufficient and disrupted.

An automatic decellularization device was developed to perfuse and decellularize male rats’ kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their efficacy in kidney decellularization and post-transplantation angiogenesis. Kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin, periodic acid Schiff, Masson’s trichrome, and Alcian blue to determine cell removal and glycogen, collagen, and glycosaminoglycan contents, respectively. Moreover, scanning electron microscopy was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quantification assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility of the decellularized scaffolds, human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) were seeded on the scaffolds. In addition, the allotransplantation was performed in back muscle and angiogenesis was evaluated. Complete cell removal in both SLES and SDS groups was observed in scanning electron microscopy and DNA quantification assays. Moreover, the extracellular matrix (ECM) architecture of rat kidney in the SLES group was significantly preserved better than the SDS group. The hUC-MSCs were successfully migrated from the cell culture plate surface into the SDS and SLES decellularized scaffolds. The formation of blood vessels was observed in the kidney in both SLES and SDS decellularized kidneys. The better preservation of ECM than SDS introduces SLES as the solvent of choice for kidney decellularization.

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease that diabetes mellitus is one of its major risk factors. MiR-126 as an endothelial cells specific miRNA plays a main role in angiogenesis. The objective of this study was to find a promising treatment by increasing therapeutic potential of adipose tissue mesenchymal stem cells (AT-MSCs) with microRNA-126 in diabetic mouse model with critical limb ischemia. AT-MSCs were isolated from male C57BL/6 mouse and characterized.The cells were infected with miR-126 recombinant lentiviral vectors. Diabetes mellitus type 1 was induced and CLI was created in the animals. Animals were divided in different groups to receive PBS, MSCs, miR-126, and MSCThe results of function scores, VEGF-A level, and histopathology data demonstrated that the miR-126 treated group was better than PBS and MSCs groups. The expression of PIK3R2 and SPRED1 were decreased in miR-126 group compared to the control group. Our results showed that MSCsThis study suggested that AT-MSCs overexpressing miR-126 could be an efficient therapeutic approach for angiogenesis in CLI with diabetes by downregulating SPRED1 and PIK3R2 and increasing secretion of angiogenic cytokines which can prolong the MSC survival.

Introduction: Critical limb ischemia (CLI) considered as the most severe form of peripheral artery disease (PAD). Current therapy for CLI are surgical reconstruction and endovascular therapy or limb amputation (for patients with no treatment options). Neovasculogenesis induced by stem cells including mesenchymal stem cells (MSCs) therapy is a promising approach to treat CLI. But this method of treatment faces challenges such as: MSCs survival and paracrine secretion. MicroRNAs are post transcriptional regulatory molecules that regulate many biological processes including VEGF pathway. MicroRNAs could be used to increase viability and angiogenic potential of MSCs. This study was conducted to reinforce and increase the angiogenic potential of BM-MSCs by using microRNA-126 and evaluate the effect of this stem cell gene therapy on treatment of ischemic tissues in CLI mouse models. Methods: BM-MSCs were isolated from male C57 BL/6 inbred mice and characterized by morphology, flow cytometry, differentiation to osteocyte and adipocyte. Transformed BM-MSCs containing miR-126 were produced by using lentiviral vector. Then femoral artery ligation and total excision of the femoral artery was performed on C57BL/6 mice to create CLI model. Animals were allocated to control, BM-MSCs, virus and BM-MSCs miR-126 groups and defined number of the cells and virus were injected 24 h after surgery. In order to determine in vitro and in vivo effects, the following tests were performed: wound healing assay, behavioral tests including: Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, real-time PCR and histological analysis. Results: Results indicated that during 28 days after transplantation, BM-MSCs and virus groups had an enhancing effect on angiogenesis. BM-MSCs miR-126 group had remarkable effect on endothelial cell migration, muscle restructure, functional improvements and neovascularization in ischemic tissues and led to more effective treatment. In vivo evaluation showed that miR-126 could increase BM-MSCs survival and paracrine secretion of angiogenic factors such as VEGF, and led to remarkable functional improvements and neovascularization in ischemic tissues. Conclusions: According to the obtained results, it could concluded that combination of BM-MSCs and miR-126 leads to more effective recovery from critical limb ischemia compared to using them alone. In fact, miR-126 can be used as a strong modifier to reinforce the angiogenic potential of BM-MSCs, leading to more effective treatment for CLI.

Introduction: Osteoarthritis (OA) as a progressive destructive disease of articular cartilage is the most common joint disease characterized by reduction of joint cartilage thickness, demolition of cartilage surface and new bone formation. To overcome these problems, the purpose of the current research was to evaluate and compare the in vivo effects of Synovial membrane-derived MSCs (SMMSCs), platelet rich plasma (PRP) and conditioned medium (secretome) on collagenase II-induced rat knee osteoarthritis (KOA) remedy. Methods: For the first step, SMMSCs were isolated and characterized. Also, secretome was collected from SMMSCs culture. Furthermore, PRP was collect from the rat heart venous blood. Second, two injection of collagenase II with an interval of 3 days was performed in the knee intra- articular space to induce osteoarthritis. Two weeks later, animals were randomly divided into 6 groups. Control group without treatment, positive group: taken an intra-articular Hyalgan injection (0.1 cc), treatment groups taken an intra-articular injection of; treatment 1: SMMSCs (5 × 106), treatment 2: SMMSCs (5 × 106) + secretome (50 µl), treatment 3: SMMSCs (5 × 106) + PRP (50 µl), and treatment 4: SMMSCs (5 × 106) + secretome (50 µl) + PRP (50 µl). Three months later, rats were sacrificed and the following assessments were executed: radiography, histopathology, and immunohistochemistry. Results: Our findings represented that a combination of the SMMSCs with PRP and secretome had a considerable effect on GAGs and collagen II contents, articular cartilage preservation, compared with other groups. In addition, combination of the SMMSCs with PRP and secretome showed the lowest expression of mmp3, while SOX9 had the highest expression in comparision with other groups. Also, SMMSCs -injected groups demonstrated better results compared with positive and control groups. Conclusions: Injection a combination of the SMMSCs with PRP and secretome resulted in better efficacy in terms of joint space width, articular cartilage surface continuity and integrity, sub chondral bone and ECM constituents such as collagen II. Indeed, transplantation of this combination could be considered as a promising therapy for patients with KOA.

Background: Chronic kidney diseases and end stage renal disease are growing threats worldwide. Tissue engineering is a new hope to surpass the current limitations such as the shortage of donor. To do so, the first step would be fabrication of an intact decellularized kidney scaffold. In the current study, an automatic decellularization device was developed to perfuse and decellularize male rats' kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their efficacy in kidney decellularization and post-transplantation angiogenesis.Methods: After anesthesia, kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin, periodic acid Schiff, Masson’s trichrome, and Alcian blue to determine cell removal and glycogen, collagen and glycosaminoglycan contents, respectively. Moreover, scanning electron microscopy was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quantification assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility and bioactivity of the decellularized scaffolds two tests were done. The scaffolds were recellularized with the human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs). In addition, the allotransplantation was performed in back muscle and angiogenesis was evaluated.Results: Complete cell removal in both SLES and SDS groups was observed in scanning electron microscopy and DNA quantification assays. Moreover, the extracellular matrix architecture of rat kidney in the SLES group was significantly preserved better than the SDS group. The hUC-MSCs were successfully migrated from the cell culture plate surface into the SDS and SLES decellularized scaffolds. The formation of blood capillaries and vessels were observed in the kidney allotransplantation in both SLES and SDS decellularized kidneys.Conclusions: We demonstrated that both SLES and SDS could be promising tools in kidney tissue engineering. The better preservation of extracellular matrix than SDS, introduces SLES as the solvent of choice for kidney decellularization.

Introduction Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment. Methods For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis. Results Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups. Conclusions Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.

Background: Osteoarthritis (OA) is a progressive degenerative disease. Previous treatment strategies have tried to slow the progress of OA. Objectives: The present study aimed to stop and reverse the progressive nature of OA by the paracrine effects of synovial stem cells. Methods: Fifty male Sprague Dawley rats were randomly allocated to five equal groups (n = 10). The control group received no treatment. The second group received an intra-articular Hyalgan injection. The third group received an intra-articular injection of secreta. The fourth group received an intra-articular injection of synovial-derived stem cells (5 × 106). The last group received an intra-articular injection of secreta combined with synovial-derived stem cells (5 × 106). Three months after treatment, the samples were harvested and evaluated by histopathological and radiological analyses. Results: Histopathological and radiological findings demonstrated significant differences between the synovial stem cell combined with the secreta group and the control and Hyalgan groups. Significant differences were observed in the subchondral bone and matrix scores between the secreta group and the synovial stem cell and Hyalgan groups (P-value = 0.042 and P-value = 0.0001, respectively). Both secreta and synovial stem cell groups showed better healing in terms of cell population viability index than the Hyalgan group (P-value = 0.015 and P-value = 0.005, respectively). The synovial stem cell combined with secreta group showed a significant difference from the synovia stem cell group in both medial femoral condyle and fabella osteophyte indices (P-value = 0.004 and P-value = 0.011, respectively). Conclusions: The group treated with synovial stem cells combined with secreta showed better outcomes than other groups in histopathological and radiological evaluations.

Chronic kidney diseases (CKD) and end stage renal disease (ESRD) are growing threats worldwide. Tissue engineering is a new hope to surpass the current limitations such as the shortage of donor. To do so, the first step would be fabrication of an intact decellularized kidney scaffold. In the current study, an automatic decellularization device was developed to perfuse and decellularize male rats' kidneys using both sodium lauryl ether sulfate (SLES) and sodium dodecyl sulfate (SDS) and to compare their efficacy in kidney decellularization and post-transplantation angiogenesis. After anesthesia, kidneys were perfused with either 1% SDS solution for 4 h or 1% SLES solution for 6 h. The decellularized scaffolds were stained with hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Masson’s trichrome, and alcian blue to determine cell removal and glycogen, collagen and glycosaminoglycans (GAGs) contents, respectively. Moreover, scanning electron microscopy (SEM) was performed to evaluate the cell removal and preservation of microarchitecture of both SDS and SLES scaffolds. Additionally, DNA quantification assay was applied for all groups in order to measure residual DNA in the scaffolds and normal kidney. In order to demonstrate biocompatibility and bioactivity of the decellularized scaffolds, allotransplantation was performed in back muscle and angiogenesis was evaluated. Complete cell removal in both SLES and SDS groups was observed in SEM and DNA quantification assays. Moreover, the extracellular matrix (ECM) architecture of rat kidney in the SLES group was significantly preservation better than the SDS group was shown. The formation of blood capillaries and vessels were observed in the kidney allotransplantations in both SLES and SDS decellularized kidneys. In conclusion, we demonstrated that both SLES and SDS could be promising tools in kidney tissue engineering. The better preservation of ECM than SDS, introduces SLES as the solvent of choice for kidney decellularization. ¬&not

Many people have irreversible defects and to be death due to burn wounds every year. The current study was conducted to assess the effects of eucalyptus essence (EE) and its mixture with licorice in burn wound healing in rats. One hundred fifty rats were divided to five equal groups. Twenty-four hours after induction of third-degree burn wound, inoculation of 108 colony-forming units of Pseudomonas aeruginosa (PA 103) into the burnt area was performed in form of subcutaneous. Group 1 was given no treatment, and group 2 received gel base. Group 3 (positive control) was treated with silver sulfadiazine (SSD). Groups 4 and 5 used EE 1% and its mixture with licorice gel 10%, respectively. After 3, 7, 14, 21, and 28 days, the animals were euthanized and the wound healing parameters were evaluated through macroscopic and microscopic examinations. Microscopically, the rats treated with EE and mixture gel showed better wound healing than SSD (P

ackground: This study aimed to compare sheep burnt wool and human amniotic membrane (AM) on second-degree burn wound healing in rats. Materials and Methods: Seventy-two adult male rats of Sprague Dawley underwent general anesthesia, and a deep second-degree burn was created on their skin by a hot iron plate. Afterward, human AM, silver sulfadiazine ointment (SSD), and sheep burned wool were used on wound area for burn treatment. On days 7, 14, and 21 of the experiment, the rats were sacrificed, and histopathological assessments were done. Results: Human AM, in comparison with other groups, significantly (P

Wound healing is a dynamic and complex process of replacing devitalized and missing cellular structures and tissue layers. Due to the importance of wound healing, this investigation was designed to compare the effect of treatment using honey and colostrum on wound-healing process in rats. In this study, 80 adult female Sprague Dawley rats were randomly divided into four groups as negative control group, groups II, III, and IV were treated by honey, bovine colostrum, and honey + colostrum, respectively. Rats were anesthetized, hair was removed from the back, and then a wound was made on the back. Visual observation, histopathological examination, and biomechanical study were performed on days 3, 7, 14, and 21 after operation. Wound area in rats which taken colostrum and honey was lower than other groups. Promotion of wound contraction and epithelialization in rats that were treated with honey and colostrum was better than the others. Biomechanical parameters in animals were treated by colostrum and honey significantly more than other rats. A combination of honey and colostrum on wounds can enhance healing better than honey and colostrum separately.

Objective: To evaluate and compare the effects of honey and fish oil on wound healing in rat. Methods: A total of 80 adult female Sprague-Dawley rats were randomly divided into four groups as negative control group, Groups II, III and IV. The rats in the four groups were treated with honey, fish oil and honey + fish oil, respectively. Rats were anesthetized, hair was removed from the back, then a wound was made on the back. Visual observation, histopathological examination and biomechanical study were performed on days 3, 7, 14 and 21 after operation. The data were analyzed using One-way ANOVA. Results: Wound area in group IV was lower than that in other groups. Promotion of wound contraction and epithelialization in group IV was better than that in other groups. Biomechanical parameters in group IV was significantly more than other rats. Conclusions: A combination of honey and fish oil on wounds can enhance healing better than honey and fish oil separately.

Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats.

Safe alternative anticoccidial drug to chemical feed additives are herbal extracts, because they don't results to tissue residue and drug resistance. In order to evaluate the effects of herbal extracts to control avian coccidiosis, 180 one-day-old broiler chickens were randomly divided into nine equal groups, as follows: (1) Biarum bovei (2) Nectaroscordum tripedale( 3) Dorema aucheri (4) Cichorium intybus (5) Prangos ferulaceae (6) diclazuril (7) Artemisia absinthium (8) infected control (9) uninfected control (each contains two groups). Administration of herbal extracts and supplementation of diclazuril was began 2 days before challenge and lasted for the duration of the experiment. The chicks of all the groups except uninfected control group were inoculated orally with sporulated oocysts (3 × 10(3) oocysts of Eimeria tenella) on the day 22 of age. The criteria employed were: body weight, feed conversion ratio, blood in feces, survival rate, lesion scoring, number of oocyst output per gram feces and histopathological changes. For histopathological evaluation, on day 12 post inoculation three birds from each group were randomly selected and humanly sacrificed. N. tripedale and diclazuril revealed better results in terms of growth performance, lesion score, extent of bloody diarrhea and oocyst count as compared to other herbal extracts. The increase in the severity of lesions was observed in groups of D. aucheri, A. absinthium, B. bovei, P. ferulaceae, C. intybus, diclazuril and N. tripedale, respectively. In conclusion, the current study showed that herbal extracts were effective in control of coccidiosis caused by the E. tenella infection.