Loaded paraquaton polymeric nanocapsules and evaluation for cardiotoxicity in Wistar rats.

Present work was conducted to prepare and evaluate, loaded paraquat nano-hydrogels using chitosan, sodium polytriphosphate, and xanthan via ionic gelification method. The fabricated L-PQ formulations were analyzed for surface morphology and functional groups using SEM and FTIR, respectively. The stability of the synthesized nanoparticle was, also, analyzed in terms of diameter size, zeta potential, dispersion index, and pH. Furthermore, the cardiotoxicity effects of the synthesized nanogels were investigated on Wistar rats in terms of enzymatic activity, echocardiographic, and histological analysis. The proper stability of the prepared formulation was also confirmed by diameter size, zeta potential, dispersion index, and pH. The efficiency of encapsulation was about 90±3.2% and the release of PQ in the loaded nanogel was about 90±2.3%. A decrease in ST (shortening time) segment by formulated PQ, either in peritoneal or gavage exposure pathway, indicates the effectiveness of the capsule layer against the penetration of toxin into the body.

Electrospun Nanofibrous Biocomposite of Royal Jelly/Chitosan/Polyvinyl Alcohol (RJ/CS/PVA) Gel as a Biological Dressing for P. aeruginosa-Infected Burn Wound.

Burn wounds are vulnerable to various infections due to damage to the tissue and changes in immune responses. Pseudomonas aeruginosa is a critical bacterium that can cause burn wound infections, which can be life-threatening and delay wound healing. Therefore, it is essential to develop an efficient strategy to prevent the spread of infection in burn wounds. The present study aims to investigate the effectiveness of electrospun nanofibers of royal jelly on a chitosan/polyvinyl alcohol polymer scaffold in repairing burn wounds infected with Pseudomonas aeruginosa. To achieve this, the researchers analyzed the morphology and physicochemical properties of the synthesized nanofibers using SEM, FTIR, BET, and TGA analyses. They also examined the antibacterial properties of the nanofibers using agar diffusion and spread plate techniques. In addition, hemolysis tests were carried out to assess biocompatibility. Finally, the ability of the nanofibers to repair burn wounds infected with Pseudomonas aeruginosa was evaluated using a laboratory mouse model. The study results showed that the synthesized nanofibers had desirable morphology and physicochemical properties and significant antibacterial effects in both in vitro and in vivo conditions. Also, loading RJ into the polymer scaffold significantly reduced erythrocyte lysis. The wound healing and contraction rates were significantly higher than the control groups, and tissue repair, re-epithelialization, and collagen synthesis occurred faster, preventing the spread of infection to deeper tissue areas. Based on these findings, the synthesized system has the potential to serve as a suitable substitute for some invasive treatments and chemical drugs to improve chronic wounds and manage infection control in burn injuries.

Cross talk of vasopressin conditioned cell therapy in ischemic heart disease: Role of oxidative stress markers.

Objectives: Background: Impaired coronary blood flow causes cardiac ischemia. Cellular therapy is a new approach to the treatment of myocardial ischemia. This study aimed to investigate the effect of adipose tissue-derived mesenchymal stem cells (AD-MSCs) conditioned with vasopressin on oxidative stress, perivascular collagen, and angiogenesis caused by myocardial infarction (MI) in rats. Materials and Methods: We divided 40 male albino Wistar rats into 4 groups; Control group; No intervention; in experimental groups, after it generated induced MI on models, it divided into three groups: Vehicle group (150 µl of cell-free culture medium received); ASC-MI group (6× 106 AD-MSC received) and AVP-ASC-MI group (received 6 × 106 AD-MSC conditioned with 10 nM vasopressin). Then, histologic parameters and anti-oxidant enzymes were evaluated 7 days post-MI cell injection. Results: Arterial muscle diameter improved and collagen deposition around the coronary arteries decreased in cell-received groups compared with the vehicle group. Malondialdehyde (MDA), catalase (CAT), (GSH) Glutathione, and Total Anti-oxidant Capacity (TAC) parameters were not significantly different between the cells received groups compared with the vehicle group. But the Catalase (CAT) parameter in the ASC-MI group had a significant increase from the control group. Conclusion: We prepared direct evidence that intramyocardial injection of AD-MSCs reveals the positive cardiac remodeling post-MI in rats, and these useful effects can be more enhanced by administrating injection of conditioned ADSCs with vasopressin.

Coactivity of Mast Cells and Stem Cells on Angiogenesis and Antioxidants' Potentials at Inflammation, Proliferation, and Tissue Remodeling Phases of Wound.

Background Reactive oxygen species cause serious damage to the physiological function of tissues. Determination of total antioxidant capacity of skin tissue is one of the determinants of damaged tissue function. Mast cells (MCs) are one of the groups of cells that are invited to the site of injury. The healing process begins with the rapid release of various types of MCs' intermediate factors at the site of injury. Bone marrow mesenchymal stem cell (BMMSC) production and secretion have been shown to regenerate the skin. The aim of this research was to evaluate the wound-healing and antioxidant effects of BMMSCs per MCs. Methods Fifty-four albino Wistar male rats were divided into three groups: (1) nonsurgery, (2) surgery, and (3) surgery + BMMSCs. Groups 2 and 3 were operated with a 3 × 8 cm flap and in group 3, cell injections (7 × 10 9 cell injection at the time of surgery) were performed. After days 4, 7, and 15, percentage of the surviving tissue, histological characteristics, superoxide dismutase (SOD) activity, and amount of malondialdehyde (MDA) were measured in the groups. For results, Graph Pad Prism 8 software was used, and data were analyzed and compared by analysis of variance and Tukey test. Results BMMSCs' application decreased the amount of MDA, increased SOD activity and survival rate of the flaps, and improved the histological characteristics. Conclusion This study revealed the protective effects BMMSCs alongside MCs against oxidative stress on the survival of the flaps. However, for clinical use, more research is needed to determine its benefits.

Resistance training and Urtica dioica increase neurotrophin levels and improve cognitive function by increasing age in the hippocampus of rats.

INTRODUCTION: Inflammation and oxidative stress are two major factors in accelerating brain aging. Consumption of some traditional herbs with antioxidant and anti-inflammatory properties such as Urtica dioica extract (Ud) and resistance training (RT) may be effective in controlling premature aging and memory impairment. Therefore, we hypothesized that the combined effect of RT and Ud might play an essential role in preventing memory disorders and hippocampal tissue changes caused by increasing age in rats. METHODS: 28 male Wistar rats (24-week) were divided into 4-groups (n = 7): control (C), Ud, RT, and Ud+RT. RT groups were trained for five weeks, and Ud extract in the 0.0166 w/v concentration (50 mg/kg, oral/daily) was administered. We also examined the effects of RT and Ud on the behavioral (memory and learning), histological (the morphological changes in the dentate gyrus), and transcript aspects of hippocampal tissue. RESULTS: Aging led to karyopyknosis in the hippocampal tissue, which was alleviated by RT and Ud supplementation. RT and Ud were accompanied by increased GPx, GSH, GAP-43, and decreased CAP-1 levels in the hippocampus. Moreover, RT and Ud led to increased NGF, BDNF, and GAP-43 levels, decreased MDA, and protection of hippocampal tissue from karyopyknosis, which was associated with cognitive improvement. However, these interventions had no significant effect on the hippocampal levels of IL-1ß, SOD, and CAT. CONCLUSIONS: These findings suggest that increasing age decreases hippocampal NGF, BDNF, and GAP-43 levels and impairs cognition, which may be reversed by regular RT and Ud extract.

Effect of fluoxetine treatment on neurotoxicity induced by lysolecithin in male rats.

Demyelination disorder is an unusual pathologic event, which occurs in the central nervous system (CNS). Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects the CNS, and it is the leading cause of disability in young adults. Lysolecithin (LPC) is one of the best toxin-induced demyelination models. In this study, a suitable model is created, and the effect of fluoxetine treatment is examined on this model. In this case, it was assumed that daily fluoxetine treatment had increased the endogenous remyelination in the LPC model. This study was focused on investigating the influence of the fluoxetine dose of 5 or 10 mg/kg per day for 1 and 4 weeks on LPC-induced neurotoxicity in the corpus callosum region. It was performed as a demyelinating model in male Wistar rats. After 3 days, fluoxetine was injected intraperitoneally (5 or 10 mg/kg per day) for 1 and 4 weeks in each group. After completing the treatment course, the corpus callosum was removed to examine the gene expression and histological analysis was performed. The results of the histopathological study of hematoxylin and eosin staining of the corpus callosum showed that in 1 and 4-week treatment groups, fluoxetine has reduced the level of inflammation at the LPC injection site (5 and 10 mg/kg per day). Fluoxetine treatment in the luxol fast blue (LFB) staining of the corpus callosum has been led to an increase in myelination capacity in all doses and times. The results of the genetic study showed that the fluoxetine has significantly reduced the expression level of tumor necrosis factor-α, nuclear factor κß, and induced nitric oxide synthase in comparison with the untreated LPC group. Also, the fluoxetine treatment has enhanced the expression level of the forkhead box P3 (FOXP3) gene in comparison with the untreated group. Fluoxetine has increased the expression level of myelination and neurotrophic genes such as myelin basic protein (MBP), oligodendrocyte transcription factor 2 (OLIG2), and brain-derived neurotrophic factor (BDNF). The outcomes demonstrated that fluoxetine reduces inflammation and strengthens the endogenous myelination in the LPC-induced demyelination model; however, supplementary studies are required for specifying the details of its mechanisms.

Applying Vasopressin-Pre-Conditioned Human Adipose Mesenchymal Stem Cells Improves Heart Condition after Transplantation into Infarcted Myocardium.

Transplantation of H-AdMSCs may improve heart function after MI. AVP is a neurohypophyseal hormone that reduces cardiovascular damage. This study investigated the role of AVP preconditioning in the survival of MSCs and their effect on myocardial repair in the MI rats. H-AMSCs were isolated and incubated for 3 days. The expression of oxytocin and vasopressin receptors was evaluated by Real-time-PCR. Forty male Wistar rats were divided into 4 groups: control, sham, ASC and AVP-ASC. Ischemia was established by ligation of LAD coronary artery. Electrocardiography, fibrosis, angiogenesis, and apoptosis in myocardium were determined after 7 days. Results showed that preconditioned MSCs significantly increased cardiac function when compared with group that received non-preconditioned MSCs. This was associated with significantly reduced fibrosis, increased vascular density, and decreased resident myocyte apoptosis. Results indicate that AVP preconditioned MSCs can be consider a novel approach to management of MI.

Effect of Bone Marrow Mesenchymal Stem Cell Sheets on Skin Capillary Parameters in a diabetic wound model: A Novel Preliminary Study

Background: Treatment with BMMSCs has anti-inflammatory, tissue regenerative, angiogenic, and immune-stimulating effects. When using as sheets or accumulate, BMMSCs causes the development of neoangiogenesis in damaged skin tissue. Diabetes, a metabolic disorder, can negatively affect many physiological functions, including the process of skin injury repair. This adverse impact may increase the risk of skin surgery. RSF is commonly used in reconstructive surgery. The terminal part of the RSF is often affected by necrosis because of impaired blood flow, which is exacerbated in diabetes. This study investigated the effect of stem cells, applied as accumulated or cell sheets, along with RSF surgery on skin capillaries in STZ-induced diabetic rats. Methods: Thirty male Wistar rats were divided into three groups (n = 10): diabetes-RSF control, diabetes-RSF local applied stem cells (loc-BMMSCs), diabetes-RSF applied stem cells as accumulated or cell sheets (ac-BMMSCs). Two weeks after the STZ injection, RSF surgery and stem cell therapy (6 × 109) were carried out (day zero). Furthermore, stereological methods were used to investigate the capillary patterns among the groups. Anti-CD31/PCAM1 immunohistochemistry was also used for further confirmation of changes in capillary parameters. Results: The results demonstrated that capillaries were protected by MSC sheets in the flap tissue, and the thickness of the epidermal layer was improved, indicationg the possible beneficial effects of MSC sheets on diabetic wound treatment. Conclusion: Stem cells, as ac-BMMSCs, may decrease the levels of wound healing complications in diabetes and can be considered as a cell therapy option in such conditions.

Aerobic Exercise-Assisted Cardiac Regeneration by Inhibiting Tryptase Release in Mast Cells after Myocardial Infarction.

BACKGROUND: Cardiovascular disease (CVD) contributes critically to the mortality, morbidity, and economic problem of illness globally. Exercise is a share of everyone's life. Some evidence-based studies have frequently shown a progressive correlation between physical activity and good health. OBJECTIVE: The effects of daily exercise on cardiomyocyte size, collagen content (fibrosis), and releasing mast cells (MCs') tryptase of the model of myocardial infarction (MI) were assessed. METHODS: 40 rats were coincidentally spread into sham+inertia (control), sham+exercise, infarction+inertia, and infarction+exercise groups. An experimental model of acute MI was induced in infarction groups. One week after surgery, exercising groups were allowed to an aerobic exercise program for six weeks. At the endpoint of the study, all examinations were performed. RESULTS: We found lesser fibrosis in sham+exercise and infarction+exercise groups compared to sham+inertia and infarction+inertia groups, respectively (p = 0.023, p = 0.001). Also, infarction groups were significantly lower than sham groups (p < 0.05) and the infarction+exercise group was significantly lower than the infarction+inertia group (p < 0.05). The effect of exercise on MCs while increased MC density and degranulation occur at the site of fibrosis, we demonstrated that exercise decreases both total MC density and degranulation in both sham and infarction groups (p < 0.05). Immunohistochemistry examinations were significantly higher expression of MCs' tryptase in infarction groups than sham groups (p < 0.05, p < 0.0001). CONCLUSION: Exercise improves fibrosis and cardiac function in both healthy and MI rats by inhibiting released MCs' tryptase.

Exercise and Urtica dioica extract ameliorate hippocampal insulin signaling, oxidative stress, neuroinflammation, and cognitive function in STZ-induced diabetic rats.

INTRODUCTION: Diabetes mellitus is related to cognitive impairments and molecular abnormalities of the hippocampus. A growing body of evidence suggests that Urtica dioica (Ud) and exercise training (ET) have potential therapeutic effects on diabetes and its related complications. Therefore, we hypothesized that the combined effect of exercise training (ET) and Ud might play an important role in insulin signaling pathway, oxidative stress, neuroinflammation, and cognitive impairment in diabetic rats. METHODS: Forty animals were divided into five groups (N = 8): healthy-sedentary (H-sed), diabetes-sedentary (D-sed), diabetes-exercise training (D-ET), diabetes-Urtica dioica (D-Ud), diabetes-exercise training-Urtica dioica (D-ET-Ud). Streptozotocin (STZ) (Single dosage; 45 mg/kg, i.p.) was used to induce diabetes. Then, ET (moderate intensity/5day/week) and Ud extract (50 mg/kg, oral/daily) were administered for six weeks. We also investigated the effects of ET and Ud on cognitive performance (assessed through Morris Water Maze tests), antioxidant capacity, and lipid peroxidation markers in hippocampus. Furthermore, we measured levels of insulin sensitivity and signaling factors (insulin-Ins, insulin receptor-IR and insulin-like growth factor-1 receptor-IGF-1R), and neuroinflammatory markers (IL-1 ß, TNF-α). This was followed by TUNEL assessment of the apoptosis rate in all regions of the hippocampus. RESULTS: D-sed rats compared to H-sed animals showed significant impairments (P < 0.001) in hippocampal insulin sensitivity and signaling, oxidative stress, neuroinflammation, and apoptosis, which resulted in cognitive dysfunction. Ud extract and ET treatment effectively improved these impairments in D-ET (P < 0.001), D-Ud (P < 0.05), and D-ET-Ud (P < 0.001) groups compared to D-sed rats. Moreover, diabetes mediated hippocampal oxidative stress, neuroinflammation, insulin signaling deficits, apoptosis, and cognitive dysfunction was further reversed by chronic Ud+ET administration in D-ET-Ud rats (P < 0.001) compared to D-sed animals. CONCLUSIONS: Ud extract and ET ameliorate cognitive dysfunction via improvement in hippocampal oxidative stress, neuroinflammation, insulin signaling pathway, and apoptosis in STZ-induced diabetic rats. The results of this study provide new experimental evidence for using Ud+ET in the treatment of hippocampal complications and cognitive dysfunction caused by diabetes.

Co- localization of Flt1 and tryptase of mast cells in skin wound of rats with type I diabetes: Initial studies.

Random skin flap (RSF) is commonly used in plastic and reconstructive surgery, but its distal part often occurs ischemia. Type 1 Diabetes mellitus (T1DM), may be detrimental for flap survival by provide sever ischemia. We sought to determine the influence of DM on the relation between mast cells and angiogenesis by examining tryptase and Fms-like tyrosine kinase 1 (Flt-1), a well-known vascular endothelial growth factor receptor (VEGFR-1), in the surviving areas of RSF in healthy and diabetic rats. 16 male rats divided into healthy and diabetic groups. T1DM was created in the diabetic rats, followed by generation of a RSF in both the control and diabetic rat. On day 7, the surviving areas of each RSF were recorded. Then animals were euthanized, and numbers of vessels, mast cells and co-localization of mast cell tryptase and Flt-1 were analyzed. T1DM decreased survival areas in the RSF compared to the healthy rats, with higher percentage of intact and degranulated mast cells. T1DM elevated the expression percentage of tryptase and VEGFR-1in the proximal and middle areas of the survival parts of the RSF in most diabetic rats. Generally, our results showed that mast cell degranulation might have a positive correlation with VEGFR-1 and in this current model of ischemic tissue in diabetic rats, this finding could lead to poor angiogenesis and weakened blood vessel function, which might result in decreased RSF survival. Additional molecular mechanisms that pertain to the effects of DM on ischemic tissues healing such as this RSF model should be determined by further investigations.

Preparation and characterization of loaded paraquat- polymeric chitosan/xantan/tripolyphosphate nanocapsules and evaluation for controlled release.

PURPOSE: Paraquat is an effective, non-selective, and fast-acting contact herbicide that is widely used. Its high solubility in water and adsorption in soil can easily poison the non-target organs. In this study, paraquat nano-hydrogels was synthesized using chitosan. METHODS: Sodium tripolyphosphate and xanthan via iononic gellification method. After preparation the loaded paraquat formulations, to verify the morphology and analysis the functional groups on the formulation, SEM and FTIR analysis were used, respectively. In this work, stability of the formulation was measured in terms of size distribution, surface charge, and pH values. To determine the release kinetics, a dialysis bag was used. In addition, herbicidal activity of the prepared formulation was tested on corn bushes and wild mustard. RESULTS: From the analysis, FT-IR spectra confirmed the hydrogel formation, and SEM images showed a dense structure in the synthesized hydrogel. According to the results of size distribution, surface charge, dispersion index and pH, it was proved that the prepared hydrogel was stable. The optimal values of chitosan, SPP, xanthan, and PQ were 0.3, 0.1, 0.15, and 20 mg, respectively. Based on the peppas equation, about 89.82% of the paraquat was released from the formulation with a paraquat loading of 89.1 ± 4.6%. CONCLUSIONS: The effect of loaded paraquat formulations on mustard and corn plants showed that the herbicidal properties of the encapsulated paraquat were preserved. This study reveal that the loaded paraquat L-PQ is a stable formulation with less toxicity effects.

Effects of endurance exercise and Urtica dioica on the functional, histological and molecular aspects of the hippocampus in STZ-Induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Many body systems and organs, including the hippocampus, are affected by diabetes, and undergo changes that may increase the risk of cognitive decline. Urtica dioica (UD) has long been recognized as a medicinal plant with beneficial effects on blood glucose control in diabetes. AIM OF THE STUDY: The present study aimed to investigate the effect of endurance exercise (Ex), along with Urtica dioica (UD) hydro-alcoholic extract on some functional, histological, and molecular aspects of the hippocampus in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: 60 male Wistar rats were divided into five groups (N = 12): healthy control (H-C), diabetes control (D-C), diabetes exercise (D-Ex), diabetes Urtica dioica (D-UD), and diabetes exercise Urtica dioica (D-Ex-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the injection by STZ, Ex (moderate intensity/5day/week) and gavage of UD extract (50mg/kg/day) was performed for six weeks. Cognitive functions were evaluated by the Morris Water Maze test, routine histological examination, and molecular studies were done via Hematoxylin & Eosin stain, and Western blot. RESULTS: Diabetic rats showed spatial learning and memory deficits, as well as negatively affects to the tissue and structure of the hippocampus in the dentate gyrus (DG) and cornu ammonis (CA) areas. Ex + UD treatment caused a decrease of neural disorganization, an increase of neural-microglial density, and thickness of the pyramidal-molecular layer in the hippocampus. In addition, Ex + UD caused a rise of GAP-43 protein levels, a reduction of CAP-1 protein levels, improved hippocampal structure, and improved learning and memory function. CONCLUSIONS: These results show that Ex, along with the UD extract, may decrease levels of the central neural complications of diabetes. Given the importance of recognizing non-pharmacological complementary therapies in this field, future studies are warranted.

Effect of Mesenchymal Stem Cells and Chicken Embryo Extract on Flap Viability and Mast Cells in Rat Skin Flaps.

Study Objective: We investigated the effect of bone marrow mesenchymal stem cells (BMMSCs) and chicken embryo extract (CEE), alone and in combination, on tissue viability of skin flaps, and mast cells (MCs), in an experimental random skin flap (RSF) rat model. Materials and Methods: A 30 mm × 80 mm RSF was made on the dorsum of each of the forty rats, which were then divided into four groups. One group did not receive any treatment and served as the control, the second group received BMMSCs, the third group received CEE + BMMSCs, and the fourth group received CEE. For BMMSC treatment, 6 × 109 BMMSCs were injected into twelve separate injection sites of each flap. Seven days after RSF surgery, the remaining viable part of each flap was measured and examined to determine the number of blood vessels, MCs, and degranulated MCs. Results: The CEE, CEE + BMMSC, and BMMSC groups displayed significantly higher levels of flap viability (ANOVA test: p = 0.000; LSD test for all groups: p = 0.000), and a greater number of vessels (ANOVA test: p = 0.000; LSD test: p = 0.000, 0.002, and 0.012, respectively), compared with the control group. The flap viability was poorer in the BMMSC group than in the CEE and CEE + BMMSC groups. The BMMSC group also had a greater number of degranulated and total MCs, compared with the CEE and CEE + BMMSC groups. Conclusions: We observed biostimulatory effects of BMMSCs, CEE, and CEE + BMMSCs on flap viability and vessel numbers, compared to the control group. MCs produced in response to BMMSC treatment have an inhibitory effect on the RSFs survival in an ischemic tissue model.

Mesenchymal stem cells improve survival in ischemic diabetic random skin flap via increased angiogenesis and VEGF expression.

Random skin flaps (RSFs) are cutaneous flaps. Despite the negative impact of diabetes mellitus (DM) on RSF viability, they are commonly used in diabetic patients. In this study, we have assessed bone marrow mesenchymal stem cell (BMMSC) treatment on RSF survival, tensiometrical parameters, angiogenesis, and mast cells (MCs) count in an ischemic RSF model in rats with type 1 DM (T1DM). We induced T1DM in 30 Wistar adult male rats. The animals were assigned to three groups of 10 rats per group as follows: group 1 (control); group 2 (placebo), and group 3 (BMMSCs). A 30 × 80 mm RSF was created in each rat. On day 7, we measured the viable portion of each RSF. A sample was taken for histological and immunohistochemistry studies, fibroblasts, MCs, angiogenesis, collagen bundle density, and the presence of vascular endothelial growth factor (VEGF)+ cells. An additional sample was taken to evaluate the flap's incision strength. Treatment with BMMSCs (17.8 ± 0.37) significantly increased RSF survival compared with the control (13.3 ± 0.35) and placebo (16.1 ± 0.27) groups (one-way analysis of variance, P = .000; least significant difference, P = .000, P = .002). There was a significant improvement in angiogenesis, as confirmed by stereologic examination. Assessment of VEGF+ cells showed prominent neovascularization in BMMSC-treated RSFs compared with the control and placebo groups. Subdermal injection of BMMSC significantly increased ischemic RSF survival as a result of stimulated neovascularization in T1DM rats. Treatment of diabetic RSF with BMMSCs showed no beneficial effects in the fibroblast number and biomechanical parameters for the repair of ischemic wounds in the rat model. Treatment with BMMSCs significantly increased collagen bundle density.

Skin Mast Cell Promotion in Random Skin Flaps in Rats using Bone Marrow Mesenchymal Stem Cells and Amniotic Membrane

Background: Skin flap procedures are employed in plastic surgery, but failure can lead to necrosis of the flap. Studies have used bone marrow mesenchymal stem cells (BM-MSCs) to improve flap viability. BM-MSCs and acellular amniotic membrane (AAM) have been introduced as alternatives. The objective of this study was to evaluate the effect of BM-MSCs and AAM on mast cells of random skin flaps (RSF) in rats. Methods: RSFs (80 × 30 mm) were created on 40 rats that were randomly assigned to one of four groups, including (I) AAM, (II) BM-MSCs, (III) BM-MSCs/AAM, and (IV) saline (control). Transplantation was carried out during the procedure (zero day). Flap necrosis was observed on day 7, and skin samples were collected from the transition line of the flap to evaluate the total number and types of mast cells. The development and the total number of mast cells were related to the development of capillaries. Results: The results of one-way ANOVA indicated that there was no statistically significant difference between the mean numbers of mast cell types for different study groups. However, the difference between the total number of mast cells in the study groups was statistically significant (p = 0.001). Conclusion: The present study suggests that the use of AAM/BM-MSCs can improve the total number of mast cells and accelerate the growth of capillaries at the transient site in RSFs in rats.

Effects of Acellular Amniotic Membrane Matrix and Bone Marrow-Derived Mesenchymal Stem Cells in Improving Random Skin Flap Survival in Rats.

BACKGROUND: The necrotic skin flap represents a great challenge in plastic and reconstructive surgery. In this study, we evaluated the effect of bioscaffolds, acellular amniotic membranes (AAMs), and bone marrow-derived mesenchymal stem cells (BM-MSCs) on random skin flap (RSF) survival in rats by applying a cell-free extracellular matrix scaffold as a supportive component for the growth and proliferation of BM-MSCs on RSFs. AAM matrix scaffolds were created by incubating AMs in ethylenediaminetetraacetic acid 0.05% at 37°C, and cell scrapers were used. OBJECTIVES: The aim of the present study was to assess the effect of AAM as a scaffold in TE, and combined with transplanted BM-MSCs, on the survival of RSFs and on the biomechanical parameters of the incision-wound flap margins 7 days after flap elevation. MATERIALS AND METHODS: BM-MSCs and AAMs were transplanted into subcutaneous tissue in the flap area. On the 7th postoperative day, the surviving flap areas were measured using digital imaging software, and the flap tissue was collected for evaluation. Forty rats were randomly divided into four groups of 10 each: group 1 received an AAM injection; group 2 underwent BM-MSC transplantation; group 3 received both AAM injection + BM-MSC transplantation; and group 4 was the control group, receiving only saline. RESULTS: The survival area in the AAM/BM-MSC group was significantly higher than in the control group (18.49 ± 1.58 versus 7.51 ± 2.42, P < 0.05). The biomechanical assessment showed no significant differences between the experimental groups and the control group (P > 0.05), and there was no correlation with flap survival. CONCLUSIONS: Our findings showed that the treatment of flaps with BM-MSC and AAM transplantations significantly promoted flap survival compared to a control group. The viability of the flap was improved by combining BM-MSCs with AAM matrix scaffolds.

Improved viability of random pattern skin flaps with the use of bone marrow mesenchymal-derived stem cells and chicken embryo extract.

OBJECTIVES: Covering tissue defects using skin flaps is a basic surgical strategy for plastic and reconstructive surgery. The aim of this study was to evaluate the effects of chicken embryo extract (CEE) and bone marrow derived mesenchymal stem cells (BM-MSCs) on random skin flap survival (RSF) in rats. Using chicken embryo extract can be an ideal environment for the growth and proliferation of transplanted cells. MATERIALS AND METHODS: Forty albino male Wistar rats were divided into 4 groups; each group consisted of 10 rats. BM-MSCs and CEE were transplanted into subcutaneous tissue in the area, where the flap would be examined. On the 7(th) postoperative day, the survival areas of the flaps were measured by using digital imaging with software assistance, and tissue was collected for evaluation. RESULTS: Survival area was 19.54±2 in the CEE group and 17.90±2 in the CEE/BM-MSC group when compared to the rates of the total skin flaps, which were significantly higher than the control group (13.47±2) (P<0.05). The biomechanical assessment showed a slight difference, although there was no statistically significant difference between the experimental groups and the control group (P>0.05). CONCLUSION: The findings from this study demonstrated that in operative treatment with BM-MSCs and CEE transplantation could promote flap survival, but the biomechanical parameters were not contrasted with a saline injection.