Plasma-derived extracellular vesicles improve mice embryo development.

BACKGROUND: To investigate the effect of plasma-derived extracellular vesicles (EVs) or conventional medium in fertilization and early embryo development rate in mice. METHODS AND RESULTS: MII oocytes (matured in vivo or in vitro conditions) were obtained from female mice. The extracellular vesicles were isolated by ultracentrifugation of plasma and were analyzed and measured for size and morphology by dynamic light scattering (DLS) and transmission electron microscopy (TEM). By western blotting analysis, the EVs proteins markers such as CD82 protein and heat shock protein 90 (HSP90) were investigated. Incorporating DiI-labeled EVs within the oocyte cytoplasm was visible at 23 h in oocyte cytoplasm. Also, the effective proteins in the early reproductive process were determined in isolated EVs by western blotting. These EVs had a positive effect on the fertilization rate (P < 0.05). The early embryo development (8 cell, morula and blastocyst stages) was higher in groups supplemented with EVs (P < 0.01). CONCLUSION: Our findings showed that supplementing in vitro maturation media with EVs derived- plasma was beneficial for mice's embryo development.

17ß-Estradiol-Loaded Exosomes for Targeted Drug Delivery in Osteoporosis: A Comparative Study of Two Loading Methods.

Purpose: Exosomes are natural nanoparticles that participate in intercellular communication through molecular transport. Recently, due to their membrane vesicular structure and surface proteins, exosomes have been used extensively in the research field of drug delivery. Osteoporosis is an inflammation in which the cellular balance of bone tissue is disturbed that reduces bone density and making bone prone to abnormal fractures with small amount of force. Utilizing estrogen is one of the main therapeutic strategies for osteoporosis. Despite the positive effects of estrogen on bone tissue, changes in the natural estrogen levels of the body can cause a number of diseases such as different types of cancer. Therefore, designing a therapeutic system which controls more accurate tissue targeting of estrogen seems to be a rational and promising practical approach. Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs)-derived exosomes were loaded by estradiol using two different methods of drug loading, namely incubation and sonication methods and then the survival effects of the drug loaded exosomes on BMMSCs was investigated. Results: Examination of size, shape, and surface factors of exosomes in different states (pure exosomes and drug-loaded exosomes) showed that the round morphology of exosomes was preserved in all conditions. However, the particles size increased significantly when loaded by sonication method. The increased survival of BMMSCs was noted with estradiol-loaded exosomes when compared to the control group. Conclusion: The results suggest that estradiol-loaded exosomes have potential to be used as nano-drug carriers in the treatment of osteoporosis.

Forskolin Improves Male Reproductive Complications Caused by Hyperglycemia in Type 2 Diabetic Rats.

BACKGROUND: In many diabetic patients, spermatogenesis complications are frequent causing infertility problems. This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes. MATERIALS AND METHODS: In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for one month and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats with more than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided into four groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2 (G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphate buffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month. RESULTS: In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly: The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Bax gene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone (P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008), sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 gene expression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values that was significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantly improved these abnormal changes in Forskolin-treated group. CONCLUSION: Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improves sperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

Bone marrow mesenchymal stem cells' osteogenic potential: superiority or non-superiority to other sources of mesenchymal stem cells?

Skeletal problems are an increasing issue due to the increase in the global aging population. Different statistics reports show that today, the global population is aging that results in skeletal problems, increased health system costs, and even higher mortality associated with skeletal problems. Common treatments such as surgery and bone grafts are not always effective and in some cases, they can even cause secondary problems such as infections or improper repair. Cell therapy is a method that can be utilized along with common treatments independently. Mesenchymal stem cells (MSCs) are a very important and efficient source in terms of different diseases, especially bone problems. These cells are present in different tissues such as bone marrow, adipose tissue, umbilical cord, placenta, dental pulp, peripheral blood, amniotic fluid and others. Among the types of MSCs, bone marrow mesenchymal stem cells (BMMSCs) are the most widely used source of these cells, which have appeared to be very effective and promising in terms of skeletal diseases, especially compared to the other sources of MSCs. This study focuses on the specific potential and content of BMMSCs from which the specific capacity of these cells originates, and compares their osteogenic potential with other types of MSCs, and also the future directions in the application of BMMSCs as a source for cell therapy.

Bone marrow mesenchymal stem cell's exosomes as key nanoparticles in osteogenesis and bone regeneration: specific capacity based on cell type.

Today, communities and their health systems are facing with several challenges associated with the population ageing. Growing number of bone disorders is one of the most serious consequences of aging. According to the reports bone disorders won't just affect the elderly population. Mesenchymal stem cells (MSCs) are multipotent cells that could be derived from a variety of tissues including bone marrow, Wharton's Jelly, adipose tissue, and others. MSCs have been utilized in different researches in the field of regenerative medicine because of their immunosuppression and anti-inflammatory mechanisms (like: inhibiting the activity of antigen presenting cells, and suppressing the activity of T lymphocyte cells, macrophages, and so on.), migration to injured areas, and participation in healing processes. Bone marrow mesenchymal stem cells (BMMSCs) are a type of these cells which can be commonly used in bone research with the promising results. These cells function by releasing a large number of extracellular vesicles (EVs). Exosomes are the most major EVs products produced by BMMSCs. They have the same contents and properties as their parent cells; however, these structures don't have the defects of cell therapy. Proteins (annexins, tetraspannins, etc.), lipids (cholesterol, phosphoglycerides, etc.), nucleic acids (micro-RNAs, and etc.) and other substances are found in exosomes. Exosomes affect target cells, causing them to change their function. The features of BMMSC exosomes' mechanism in osteogenesis and bone regeneration (like: effects on other MSCs, osteoblasts, osteoclasts, and angiogenesis) and also the effects of their micro-RNAs on osteogenesis are the subject of the present review.

The effects of metformin and forskolin on sperm quality parameters and sexual hormones in type II diabetic male rats.

This study aimed to investigate the effects of metformin and forskolin independently and in combinations on the sperm quality parameters and sexual hormones of diabetic male rats. Fifty adult male rats were divided randomly into five identical groups, and diabetes mellitus was induced to the rats, except for the rats in the control group, using a high-fat diet and injection of Streptozotocin. Daily administration of metformin and forskolin independently and in combinations were performed for 8 weeks in different groups. Sperm quality parameters (including sperm count, morphology, sperm motility and Johnson score), testosterone, blood sugar level, Bax to Bcl-2 ratio mRNA expression level and oxidative stress levels were measured and compared between the investigated groups. Treating diabetic rats with metformin and forskolin resulted in significant improvement in sperm quality parameters, increased testosterone levels, reduced oxidative stress in blood and testicular tissue, and decreased blood sugar, and Bax to Bcl-2 ratio level. Although the combination of metformin with forskolin had a higher effect in some parameters such as testosterone levels compared to treatment with metformin or forskolin alone, this combination had not shown a synergistic effect in all the sperm quality parameters. Metformin and forskolin are effective anti-diabetic agents, which significantly improve the sperm quality and sexual hormone levels in diabetic rats. Combining metformin and gorskolin resulted in significantly better testosterone level and antioxidant activity in blood serum without significant effect on sperm quality of diabetic rats.

Preconditioning with SDF-1 Improves Therapeutic Outcomes of Bone marrow-derived Mesenchymal Stromal Cells in a Mouse Model of STZ-induced Diabetes.

BACKGROUND: Nowadays, transplantation of Bone marrow-derived Mesenchymal Stromal Cells (BMSCs) is currently an important alternative therapy for patient's type 1 diabetes mellitus. But a number of critical obstacles lie ahead of this new strategy including reducing stem cell homing to the damaged tissue due to oxidative stress. The purpose of the present study was to investigate whether preconditioning of BMSCs with SDF-1 could enhance their homing to the pancreas and promote regeneration of the pancreatic ß cells after being intravenously injected. METHODS: Mice BMSCs were isolated and expanded. Cell proliferation was assayed by MTT Assay. Preconditioning was performed with 10 ng/ml SDF-1α for 24 hr. Male NMRI mice were injected with high-dose STZ (150 mg/kg). The preconditioned or un-preconditioned BMSCs at a dose of 1×106 cells were infused via the tail vein. Blood and pancreatic tissue samples were taken from all mice for flow cytometry, biochemical and histological studies. RESULTS: Proliferation and homing of BMSCs to the pancreas were significantly increased in the BMSCs with SDF-1α preconditioning. Differentiation of transplanted BMSCs, were significantly increased in preconditioning group. Although BMSCs without SDF-1 preconditioning exhibited remarkable recovery of pancreatic islets structure but this recovery were significantly increased in the BMSCs with SDF-1α preconditioning. CONCLUSION: Our results showed the effectiveness of SDF-1α preconditioning in BMSCs transplantation of STZ induced diabetes mice which might be achieved through improvement of BMSCs homing into the injured pancreas.