Effect of hydro-alcoholic extract of Olea europaea on apoptosis-related genes and oxidative stress in a rat model of torsion/detorsion-induced ovarian damage

Objective: To evaluate the impact of Olea (O.) europaea extract on markers of oxidative stress and apoptosis of ovarian tissues in a rat model of torsion/detorsion-induced ovarian damage. Methods: A total of 28 Wistar female rats were randomly assigned into 4 groups, with 7 rats in each group. The sham group received a 2.5 cm longitudinal incision in the midline part of the abdomen which was then sutured with 5-0 nylon thread;the torsion/detorsion group underwent torsion induction for 3 h followed by reperfusion for 10 days;the torsion/detorsion+O. europaea group received 300 mg/kg hydro-alcoholic extract of O. europaea 30 min before detorsion, followed by reperfusion for 10 days;and the O. europaea group only received 300 mg/kg hydro-alcoholic extract of O. europaea for 10 days. After the treatment period, blood samples were taken;the levels of estrogen, glutathione peroxidase, superoxide dismutase, and malondialdehyde were assayed. The histological changes, as well as the rate of apoptosis in ovarian tissues, were also carried out by histomorphometric analysis at day 10 post-procedure. Results: Histological comparisons demonstrated a significant detrimental change in the torsion/detorsion group as compared with other groups. The number of pre-antral and antral follicles and corpus luteum was significantly decreased in the torsion/detorsion group compared with the sham group, while treatment with O. europaea could enhance their numbers (P<0.05). The index of apoptosis and the number of atretic body in the ovarian tissue were significantly higher in the torsion/detorsion group compared with the sham group (P<0.05). The concentrations of glutathione peroxidase, estrogen, and superoxide dismutase as well as the mRNA expression of Bcl-2 were considerably diminished in the torsion/detorsion group while they were elevated in the torsion/detorsion+O. europaea group (P<0.05) compared with the torsion/detorsion group. The serum malondialdehyde level and the mRNA expression of Bax were markedly increased during ischemia, while treatment with O. europaea significantly diminished the increased concentrations of malondialdehyde and Bax level in the torsion/detorsion+O. europaea group (P<0.05). Conclusions: O. europaea extract can reduce the degree of tissue damage induced by oxidative stress and apoptosis in the ovary following ovarian ischemia/reperfusion.

Biofabrication of size-controlled liver microtissues incorporated with ECM-derived microparticles to prolong hepatocyte function

Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidly lose their functions during ex vivo culture.Here,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug sensitivity.The results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to LM.CYP450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM group.In conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation applications.In the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.

Human Endometrial Stem Cells May Differentiate into Schwann Cells in Fibrin Gel as 3D Culture

Damage in central nervous system plays an important role in biological life and causes severe paralysis of limbs and some organs. There are solutions to problems that can be a great revolution in the transplanted spinal cord and nerve injuries. Schwann cells (SCs) have important roles in development, myelination and regeneration in the peripheral nervous system. The applications of SCs in regenerative medicine are limited because of slow growth rate and difficulties in harvesting. Critical to the hypothesis is the experimental fact that human endometrial-derived stem cells (hEnSCs) as multipotent accessible source of cells are known as useful cell candidates in the field of nerve tissue engineering. We decided to use the three-dimensional culture of Schwann cells differentiated from endometrial stem cell in fibrin gel. In this study, we investigate the expression of differentiated Schwann cell markers by exposing of endometrial stem cells with induction media including FGF2/FSK/HRG/RA. Using immunocytochemistry, we show that differentiated cells express S100 and P75 markers. These results show that for the first time, human endometrial stem cells can be differentiated into Schwann cells in 2D and 3D culture. These novel differentiated cells in fibrin gel might open new opportunities for the management of cell survival and neurotrophic potential in tissue engineering approaches for nerve repair.

Evaluating the safety and efficacy of mesenchymal stem cell-derived exosomes for treatment of refractory perianal fistula in IBD patients:clinical trial phaseⅠ

Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This study aimed to assess the safety and efficacy of usingmesenchymal stemcell(MSC)exosomes to treat refractory fistulas in patients with inflammatory bowel disease.Methods:MSCs were derived from the umbilical cords and their exosomes were isolated.Five patients with refractory perianal Crohn’s disease fistulas with amedian age of 35 years(range 31–47 years)were enrolled in the study.Exosome injections were administered in the operating roomto patients with refractory fistula(fistulas that are irresponsive to anti-tumor necrosis factor-αadministration within 6months).Sixmonths later,a physical examination,face-to-face interviews,andmagnetic resonance imaging were employed to evaluate the therapy responses of patients.Results:The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy.Three patients who received exosome injections exhibited complete healing,while one reported no improvement and active discharge from the fistula site.In addition,five patients(100%)reported neither systemic nor local adverse effects.Conclusions:Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect,as evidenced in this and other studies,and may play a significant role in the future treatment of gastrointestinal fistulas.

Electrospun Aloe Vera Extract Loaded Polycaprolactone Scaffold for Biomedical Applications:A Promising Candidate for Corneal Stromal Regeneration

Corneal diseases,the second leading cause of global vision loss affecting over 10.5 million people,underscores the unmet demand for corneal tissue replacements.Given the scarcity of fresh donor corneas and the associated risks of immune rejection,corneal tissue engineering becomes imperative.Developing nanofibrous scaffolds that mimic the natural corneal structure is crucial for creating transparent and mechanically robust corneal equivalents in tissue engineering.Herein,Aloe Vera Extract(AVE)/Polycaprolactone(PCL)nanofibrous scaffolds were primed using electrospinning.The electrospun AVE/PCL fibers exhibit a smooth,bead-free morphology with a mean diameter of approximately 340±95 nm and appropriate light transparency.Mechanical measurements reveal Young’s modulus and ultimate tensile strength values of around 3.34 MPa and 4.58 MPa,respectively,within the range of stromal tissue.In addition,cell viability of AVE/PCL fibers was measured against Human Stromal Keratocyte Cells(HSKCs),and improved cell viability was observed.The cell-fiber interactions were investigated using scanning electron microscopy.In conclusion,the incorporation of Aloe Vera Extract enhances the mechanical,optical,hydrophilic,and biological properties of PCL fibers,positioning PCL/AVE fiber scaffolds as promising candidates for corneal stromal regeneration.

Bioactive Materials:A Comprehensive Review on Interactions with Biological Microenvironment Based on the Immune Response

Application of“bioactive materials”,as a modified version of biomaterials,can optimize the response of the biological system due to their surface reactivity and formation of strong interactions with the adjacent tissue upon implantation.However,choosing an appropriate bioactive material that suits to the application and provides the desired mechanical,physical,chemical and biological functionality,as well as understanding the aspects of biological reaction to the biomaterial,in particular immune response,it plays a key role in successful integration of the implant.In this review,we will discuss different bioactive materials including bioactive ceramics,polymers and composites and their applications in drug delivery and scaffold preparation in order to provide an adequate introduction to the recent studies.Considering the necessity of regulation of implant fate for higher biocompatibility,the comprehensive overview to the immune response will be reviewed with the focus on representing the cell-biomaterial interactions and more importantly,the inflammatory responses.Ultimately,we will also discuss about different approaches namely as immunomodulation to elicit the desired physiochemical properties and mimicking native cellular response using bioactive compounds,functionalizing the implant surface with active molecules and alteration of the surface morphology.With better understanding of bioactive materials and their interactions with body,more novel biomaterials representing desired properties can be designed.