We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Mechanically strained osteocyte-derived exosomes contained miR-3110-5p and miR-3058-3p and promoted osteoblastic differentiations
Background
Osteocytes are critical mechanosensory cells in bone, and mechanically stimulated osteocytes produce exosomes that can induce osteogenesis. MicroRNAs (miRNAs) are important constituents of exosomes, and some miRNAs in osteocytes regulate osteogenic differentiation; previous studies have indicated that some differentially expressed miRNAs in mechanically strained osteocytes likely influence osteoblastic differentiation. Therefore, screening and selection of miRNAs that regulate osteogenic differentiation in exosomes of mechanically stimulated osteocytes are important.
Results
A mechanical tensile strain of 2500 με at 0.5 Hz 1 h per day for 3 days, elevated prostaglandin E2 (PGE2) and insulin-like growth factor-1 (IGF-1) levels and nitric oxide synthase (NOS) activity of MLO-Y4 osteocytes, and promoted osteogenic differentiation of MC3T3-E1 osteoblasts. Fourteen miRNAs differentially expressed only in MLO-Y4 osteocytes which were stimulated with mechanical tensile strain, were screened, and the miRNAs related to osteogenesis were identified. Four differentially expressed miRNAs (miR-1930-3p, miR-3110-5p, miR-3090-3p, and miR-3058-3p) were found only in mechanically strained osteocytes, and the four miRNAs, eight targeted mRNAs which were differentially expressed only in mechanically strained osteoblasts, were also identified. In addition, the mechanically strained osteocyte-derived exosomes promoted the osteoblastic differentiation of MC3T3-E1 cells in vitro, the exosomes were internalized by osteoblasts, and the up-regulated miR-3110-5p and miR-3058-3p in mechanically strained osteocytes, were both increased in the exosomes, which was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Conclusions
In osteocytes, a mechanical tensile strain of 2500 με at 0.5 Hz induced the fourteen differentially expressed miRNAs which probably were in exosomes of osteocytes and involved in osteogenesis. The mechanically strained osteocyte-derived exosomes which contained increased miR-3110-5p and miR-3058-3p (two of the 14 miRNAs), promoted osteoblastic differentiation.
Plant-derived exosome-like nanovesicles: A novel nanotool for disease therapy
Exosomes are extracellular vesicles comprising bilayer phospholipid membranes and are secreted by eukaryotic cells. They are released via cellular exocytosis, contain DNA, RNA, proteins, and other substances, and participate in various cellular communications between tissues and organs. Since the discovery of exosomes in 1983, animal-derived exosomes have become a research focus for small-molecule drug delivery in biology, medicine, and other fields owing to their good biocompatibility and homing effects. Recent studies have found that plant-derived exosome-like nanovesicles (PELNVs) exhibit certain biological effects, such as anti-inflammatory and anti-tumor abilities, and have minimal toxic side effects. Because they are rich in active lipid molecules with certain pharmacological effects, PELNVs could be novel carriers for drug delivery. In this review, the biological formation and effects, isolation, and extraction of PELNVs, as well as characteristics of transporting drugs as carriers are summarized to provide new ideas and methods for future research on plant-derived exosome-like nanovesicles.
Assessing the Efficacy of Mesenchymal Stem Cell-Derived Exosomes in Preclinical Models of Osteoarthritis
Background Osteoarthritis (OA) is a common degenerative disease that affects both people and animals, resulting in persistent pain and joint deformities. Its growing prevalence presents considerable difficulties to public health and veterinary care systems around the world. Despite substantial research, the molecular pathways underlying OA pathogenesis remain poorly understood, limiting the development of effective treatment strategies. Exosomes, or small endosomal membrane microvesicles, have emerged as intriguing vehicles for intercellular communication and medicinal administration in a variety of illnesses, including OA. However, their efficacy and methods of action in preclinical models of OA require additional exploration.
Methods
We analyzed several databases from 2016 to 2023 for original studies on exosome treatment in preclinical OA models. The inclusion criteria included studies that used exosomes generated from mesenchymal stem cells (MSCs) in both human and animal models of OA. Thematic synthesis and data extraction were used to examine research features, dosage administration techniques, and efficacy results. The quality of included studies was assessed using recognized criteria, and statistical analysis was performed to determine the efficacy of exosome treatment in decreasing Osteoarthritis Research Society International (OARSI) scores.
Results
Our study comprised thirteen peer-reviewed articles that included both human and animal models of OA. The majority of trials used bone marrow MSC-derived exosomes administered intra-articularly. The analysis of OARSI scores revealed a considerable reduction in joint deterioration following exosome therapy. Source analysis demonstrated that exosome treatment originating from human and animal MSCs was consistently effective. However, an assessment of study quality revealed potential biases and limitations, emphasizing the need for more research to validate these findings and refine therapy options for OA management.
Exosomes derived from human amniotic mesenchymal stem cells promotes angiogenesis in hUVECs by delivering novel miRNA N-194
Background To investigate the effect and mechanism of exosomes derived from human amniotic mesenchymal stem cells (hAMSC-Exos) promoting angiogenesis.
Methods HAMSC-Exos were isolated using ultracentrifugation and characterized by transmission electron microscopy, NTA, and Western blot. The uptake of hAMSC-Exos by hUVECs was analyzed using PKH-26 labeling, and the effect of hAMSC-Exos on angiogenesis was analyzed in human umbilical vein endothelial cells hUVECs by cell viability assay, Transwell migration assay, Matrigel tube formation assay, and Matrigel plug assays in nude mice. Bioinformatics methods were used to analyze miRNA high-throughput sequencing data of hAMSC-Exos, and RT-qPCR was used to validate the novel miRNAs. HAMSC-Exos with high and low N-194 expression were obtained by transfection, respectively. Target genes were predicted using TargetScan, and the mRNA and protein levels of potential target genes were analyzed by RT-qPCR and Western blot after N-194 mimics transfection. Interaction between miRNAs and target genes was detected using the dual-luciferase reporter assay. Target genes were overexpressed in hUVECs by transfection. The roles of target genes in the influence of N-194 on cell function were determined by analyzing angiogenesis.
Results The extracted hAMSC-Exos showed teato-like under transmission electron microscopy, and the NTA results showed the particle size of 115.6±38.6 nm. The positive expression of CD9, CD63, and CD81 were verified using Western blot. The treatment of hUVECs with hAMSC-Exos significantly increased cell proliferation, migration, and angiogenesis. HAMSC-Exos contained the novel miRNAs N-194, N-314, N-19, N-393, and N-481, and the expression of N-194 was higher. The Exos derived from hAMSCs which were transfected with FAM-N-194 mimics were able to deliver FAM-N-194 mimics to hUVECs. The hAMSC-Exos with high N-194 significantly promoted angiogenesis in hUVECs. N-194 mimics transfection significantly reduced mRNA and protein levels of potential target gene ING5, and N-194 mimics significantly reduced the luciferase activities expressed by wild-type reporter gene vectors for ING5. The ING5 overexpression significantly reduced the angiogenic capacity of hUVECs. ING5 overexpression suppressed the expression of HSP27 and PLCG2.
Conclusions HAMSC-Exos promotes angiogenesis in hUVECs by delivering novel miRNA N-194 which targets ING5.
The Comparative Effect of Plasma Exosomes of Young and Old People on the Expression of BCL-2 and BAX Genes in Hematopoietic Stem Cells
Apoptosis may disrupt differentiation of hematopoietic stem cells (HSCs), which can affect aging. Thus, the main goal of this study was to compare the effect of plasma exosomes from young and old people on the expression of Bcl-2-associated X (BAX) and B-cell lymphoma 2 (BCL-2) genes in the HSCs. Plasma samples were acquired from four elderly adults and four younger adults, referring to Blood Transfusion Organization of Tehran-Iran during August 2022– September 2022.Then, the exosomes of the samples were extracted and analyzed using DLS, TEM, and CD63 surface marker. HSCs were isolated from umbilical cord blood cells. The MTT test was used to assess the viability of exosomes-treated HSCs at doses of 5 and 10 μg/ml. The expression of BAX and BCL-2 genes in the cells was examined using real-time PCR. A one-way analysis of variance (ANOVA) was performed to examine the distinctions among five groups. The viability of HSCs was not affected by the exosomes from young and old people than the control group (P = 0.453). Exosomes from young people (doses 5 and 10 µg/ml) did not have any significant impacts on BAX (P = 0.746, and P = 0.345, respectively) and BCL-2 (P = 0.773, and P = 0.461, respectively) expression in the HSCs compared to the control group. The BAX gene was significantly upregulated and the BCL-2 gene was significantly downregulated after utilizing the exosomes derived from the plasma of elderly individuals (dose 10 µg/ml) compared to the control (P = 0.001, P = 0.002, respectively). The current research shows that aged people's exosomes can increase BAX/ BCL-2 ratio in umbilical cord blood-derived HSCs compared to control and young groups.
Exploring the Emerging Application Areas for Milk-derived Exosomes
In recent years, the dairy industry has witnessed a surging demand for innovative, value-added products that cater to the evolving needs of health-conscious consumers.
Among these innovations, milk-derived exosomes stand out for their exceptional stability in the gastrointestinal environment.
Naturally present in milk, these nano-sized vesicles are emerging as a promising new platform for therapeutics, nutraceuticals, and functional foods.
Discover the upcoming transformative trends with our upcoming 2024 Dairy Industry Trend Report.
Intranasal administration of umbilical cord mesenchymal stem cell exosomes alleviates Parkinson's disease
Parkinson's disease (PD) is a common and complex neurodegenerative disease. This disease is typically characterized by the formation of Lewy bodies in multiple brain regions and dopaminergic neuronal loss in the substantia nigra pars compacta, resulting in non-motor symptoms (e.g., olfactory deficits) and motor dysfunction in the late stages. There is yet no effective cure for Parkinson’s disease. Considering the neuroprotective effects of exosomes, we investigated whether intranasal administration of umbilical cord mesenchymal stem cell exosomes could improve behavioral functions in PD mice. First, exosomes were endocytosed by the cells in vitro and in vivo, indicating that exosomes can cross the blood-brain barrier. Second, we found that both motor and non-motor functions of the PD models were effectively improved during intranasal exosomes treatment. Finally, the activity of olfactory bulb neurons was improved and the loss of dopaminergic neurons in the substantia nigra pars compacta was reversed. Moreover, exosomes attenuated microglia and astrocyte activation, leading to a low level of inflammation in the brain. In conclusion, our study provided a new reference for the clinical application of exosomes in the treatment of PD.