Role Of Extracellular Vesicles Research Articles

Role of Extracellular Vesicles in Autoimmune Pathogenesis.

Autoimmune diseases are conditions that emerge from abnormal immune responses to natural parts of the body. Extracellular vesicles (EVs) are membranous structures found in almost all types of cells. Because EVs often transport “cargo” between cells, their ability to crosstalk may be an important communication pathway within the body. The pathophysiological role of EVs is increasingly recognized in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Type 1 diabetes, and autoimmune thyroid disease. EVs are considered as biomarkers of these diseases. This article outlines existing knowledge on the biogenesis of EVs, their role as messegers in cellular communication and the function in T/B cell differentiation and maturation, and focusing on their potential application in autoimmune diseases.

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies.

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and substance abuse are often comorbid, we discuss the potential role of EVs in the intersection of substance abuse and HIV. Taken together, the studies presented in this comprehensive review shed light on the potential role of EVs in the exacerbation of substance use and HIV. As a subject of growing interest, EVs may continue to provide information about mechanisms and pathogenesis in substance use disorders and CNS pathologies, perhaps allowing for exploration into potential therapeutic options.

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go.

Adenoid cystic carcinoma of the salivary gland (SACC) is a rare malignant tumors of the head and neck region, but it is one of the most common malignant tumors that are prone to perineural invasion (PNI) of the head and neck. The prognosis of patients with SACC is strongly associated with the presence of perineural spread (PNS). Although many contributing factors have been reported, the mechanisms underlying the preferential destruction of the blood-nerve barrier (BNB) by tumors and the infiltration of the tumor microenvironment by nerve fibers in SACC, have received little research attention. This review summarizes the current knowledge concerning the characteristics of SACC in relation to the PNI, and then highlights the interplay between components of the tumor microenvironment and perineural niche, as well as their contributions to the PNI. Finally, we provide new insights into the possible mechanisms underlying the pathogenesis of PNI, with particular emphasis on the role of extracellular vesicles that may serve as an attractive entry point in future studies.

Role of extracellular vesicles in nephrology. Prospective use in therapy of kidneys and urinary tract diseases

Extracellular vesicles (EVs) represent heterogeneous population of the microparticles liberated by almost all live cages which are widely investigated recently in various biological and medical areas. They usually consist of two basic types (exosomes and microvesicles) and recently draw the increasing attention in quality mesenges of the cellular alarm system. Really, these vesicles can influence on cages-recipients, transferring and delivering difficult complexes of biomolecules (the lipids, proteins, coagulation factors, antigene, nucleinic acids), protected from enzymatic to degradation in environment. Importance EVs has been shown in pathophysiology several bodies, in particular, in kidneys where various types of cages нефрона allocate EVs which mediate their communication with underlaying cages urinogenous ways. By numerous researches it is established that EVs are involved in cellular communications during the regenerative and pathological processes occurring in a kidney. During the last years also it has been proved that vesicles play an important role in normal physiology of kidneys. Though many mechanisms EVs at illnesses are still studied insufficiently, in particular, in kidneys, opening of a role of additional mechanisms can help to throw light on the biological processes proceeding in kidneys. Eventually, extracellular vesicles, allocated with nephritic cages, collect in urine, becoming, thus, the big resource as markers of illnesses urinogenous a path and the perspective noninvasive diagnostic tool at nephritic illnesses. In the present review we discuss the latest data about a role EVs in pathophysiology of kidneys and their potential prospects in diagnostics and therapy of nephritic illness.

Role of extracellular vesicles in the progression, diagnosis and treatment of thyroid cancer (Review)

Extracellular vesicles (EVs) enclose a myriad of proteins and nucleic acids that are released in the extracellular milieu of cells through EVs. These secreted molecules serve as signaling factors that can alter the biological characteristics of tumor cells. Several studies have suggested that EVs are associated with tumor proliferation, metastasis and microenvironmental regulation in thyroid carcinoma (TC). The biomolecules in EVs can serve as differential diagnostic biomarkers for TC. Moreover, EVs derived from natural killer (NK) cells can be developed as potential immunotherapeutic agents, since they can actively target and kill tumor cells in TC. Recent years have witnessed a steep rise in the number of TC cases, and thus, accurate diagnosis and novel TC treatment strategies are being actively explored. The present review discusses the recent research investigations on EVs as far as the biological, clinical diagnosis and treatment of primary TC tumors are concerned. In addition, the new opportunities and challenges encountered in the practical applications of EVs in thyroid carcinoma are outlined.

Molecular characteristics and functional differences of anti-PM/Scl autoantibodies and two other distinct and unique supramolecular structures known as "EXOSOMES".

The term "exosome" has been applied to three distinct supramolecular entities, namely the PM/Scl autoantibodies or "RNA exosomes", transforming DNA fragments termed "DNA exosomes", and small size extracellular vesicles knows as "exosomes". Some of the molecular components of the "PM/Scl exosome complex" or "RNA exosome" are recognized by specific autoantibodies present in the serum from some Systemic Sclerosis (SSc), polymyositis (PM) and polymyositis SSc (PM/Scl) overlap syndrome patients. On the other hand, one of the most active focuses of laboratory investigation in the last decade has been the biogenesis and role of extracellular vesicles known as "exosomes". The remarkable ability of these "exosome" vesicles to alter the cellular phenotype following fusion with target cells and the release of their macromolecular cargo has revealed a possible role in the pathogenesis of numerous diseases, including malignant, inflammatory, and autoimmune disorders and may allow them to serve as theranostic agents for personalized and precision medicine. The indiscriminate use of the term "exosome" to refer to these three distinct molecular entities has engendered great confusion in the scientific literature. Here, we review the molecular characteristics and functional differences between the three molecular structures identified as "exosomes". Given the rapidly growing scientific interest in extravesicular exosomes, unless a solution is found the confusion in the literature resulting from the use of the term "exosomes" will markedly increase.

Role of Extracellular Vesicles in Pulmonary Arterial Hypertension: Modulation of Pulmonary Endothelial Function and Angiogenesis.

Extracellular vesicles (EVs) have the potential to act as intercellular communicators. The aims were to characterize circulating EVs in patients with pulmonary arterial hypertension (PAH) and to explore whether these EVs contribute to endothelial activation and angiogenesis. Approach and Results: Patients with PAH (n=70) and healthy controls (HC; n=20) were included in this cross-sectional study. EVs were characterized and human pulmonary endothelial cells (hPAECs) were incubated with purified EVs. Endothelial cell activity and proangiogenic markers were analyzed. Tube formation analysis was performed for hPAECs, and the involvement of PSGL-1 (P-selectin glycoprotein ligand 1) was evaluated. The numbers of CD62P+, CD144+, and CD235a EVs were higher in blood from PAH compared with HC. Thirteen proteins were differently expressed in PAH and HC EVs, where complement fragment C1q was the most significantly elevated protein (P=0.0009) in PAH EVs. Upon EVs-internalization in hPAECs, more PAH compared with HC EVs evaded lysosomes (P<0.01). As oppose to HC, PAH EVs stimulated hPAEC activation and induced transcription and translation of VEGF-A (vascular endothelial growth factor A; P<0.05) and FGF (fibroblast growth factor; P<0.005) which were released in the cell supernatant. These proangiogenic proteins were higher in patient with PAH plasma compered with HC. PAH EVs induced a complex network of angiotubes in vitro, which was abolished by inhibitory PSGL-1antibody. Anti-PSGL-1 also inhibited EV-induced endothelial cell activation and PAH EV dependent increase of VEGF-A. Patients with PAH have higher levels of EVs harboring increased amounts of angiogenic proteins, which induce activation of hPAECs and in vitro angiogenesis. These effects were partly because of platelet-derived EVs evasion of lysosomes upon internalization within hPAEC and through possible involvement of P-selectin-PSGL-1 pathway.

Abstract 414: A Canine Myocardial Slice Model of Doxorubicin Induced Cardiotoxicity to Study Autophagy Modulation and Its Effect on Extracellular Vesicle Associated Mirna

Dogs with cancer treated with chemotherapy agents such as doxorubicin (DOX) develop cardiovascular toxicity, providing an opportunity to evaluate cardioprotective strategies in the setting of cancer treatment translatable to human disease. However, due to the lack of a suitable approach to culture primary adult canine cardiomyocytes, mechanistic interrogation of cardiotoxicity after cancer therapy remains a challenge. Our study thus aims to validate a canine myocardial slice culture model to study autophagy modulation and the role of extracellular vesicle (EV) associated miRNA in the setting of DOX induced cardiotoxicity. We hypothesize that induction of autophagy in canine myocardial tissue will reduce apoptosis, exert early changes to EVs, and ameliorate DOX cardiotoxicity. Left ventricular tissue from client-owned donated adult dog hearts was sectioned with a vibratome and viability of the cultured myocardial slices was evaluated by histology and MTT assay. Apoptosis was quantified by TUNEL, and autophagy by fluorescent LC3 protein puncta. Secreted EVs were isolated from cultured tissue by size exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy and immunoblot. Canine myocardial slices are consistently viable for 7 days in culture - cardiomyocyte morphology is maintained with low levels of apoptosis, and baseline autophagy is observed. Induction of autophagy with rapamycin treatment results in reduced apoptosis. Cardiac tissue derived extracellular vesicles showed typical size, morphology and enrichment of proteins including tetraspanin CD9 and will be evaluated for changes to EV miRNA profile with autophagy modulation. The canine myocardial slice model allows, for the first-time, the elucidation of complex cross-talk among apoptosis, autophagy, and EVs with molecular and cellular resolutions. Detecting early changes in canine cardiomyocyte autophagy to halt cardiac damage rather than managing its consequences is a paradigm shift translatable towards preventing chemotherapy associated cardiotoxicity.

Extracellular Vesicle Proteins and MicroRNAs as Biomarkers for Traumatic Brain Injury.

Traumatic brain injury (TBI) is a heterogeneous condition, associated with diverse etiologies, clinical presentations and degrees of severity, and may result in chronic neurobehavioral sequelae. The field of TBI biomarkers is rapidly evolving to address the many facets of TBI pathology and improve its clinical management. Recent years have witnessed a marked increase in the number of publications and interest in the role of extracellular vesicles (EVs), which include exosomes, cell signaling, immune responses, and as biomarkers in a number of pathologies. Exosomes have a well-defined lipid bilayer with surface markers that reflect the cell of origin and an aqueous core that contains a variety of biological material including proteins (e.g., cytokines and growth factors) and nucleic acids (e.g., microRNAs). The presence of proteins associated with neurodegenerative changes such as amyloid-β, α-synuclein and phosphorylated tau in exosomes suggests a role in the initiation and propagation of neurological diseases. However, mechanisms of cell communication involving exosomes in the brain and their role in TBI pathology are poorly understood. Exosomes are promising TBI biomarkers as they can cross the blood-brain barrier and can be isolated from peripheral fluids, including serum, saliva, sweat, and urine. Exosomal content is protected from enzymatic degradation by exosome membranes and reflects the internal environment of their cell of origin, offering insights into tissue-specific pathological processes. Challenges in the clinical use of exosomal cargo as biomarkers include difficulty in isolating pure exosomes, variable yields of the isolation processes, quantification of vesicles, and lack of specificity of exosomal markers. Moreover, there is no consensus regarding nomenclature and characteristics of EV subtypes. In this review, we discuss current technical limitations and challenges of using exosomes and other EVs as blood-based biomarkers, highlighting their potential as diagnostic and prognostic tools in TBI.

Role of Extracellular Vesicles in the Pathophysiology, Diagnosis and Tracking of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting approximately one-third of the global population. Most affected individuals experience only simple steatosis—an accumulation of fat in the liver—but a proportion of these patients will progress to the more severe form of the disease, non-alcoholic steatohepatitis (NASH), which enhances the risk of cirrhosis and hepatocellular carcinoma. Diagnostic approaches to NAFLD are currently limited in accuracy and efficiency; and liver biopsy remains the only reliable way to confirm NASH. This technique, however, is highly invasive and poses risks to patients. Hence, there is an increasing demand for improved minimally invasive diagnostic tools for screening at-risk individuals and identifying patients with more severe disease as well as those likely to progress to such stages. Recently, extracellular vesicles (EVs)—small membrane-bound particles released by virtually all cell types into circulation—have emerged as a rich potential source of biomarkers that can reflect liver function and pathological processes in NAFLD. Of particular interest to the diagnosis and tracking of NAFLD is the potential to extract microRNAs miR-122 and miR-192 from EVs circulating in blood, particularly when using an isolation technique that selectively captures hepatocyte-derived EVs.

The Role of Extracellular Vesicles in β-Cell Function and Viability: A Scoping Review.

Extracellular vesicles (EVs) released by cells throughout the body have been implicated in diabetes pathogenesis. Understanding the role of EVs in regulation of β-cell function and viability may provide insights into diabetes etiology and may lead to the development of more effective screening and diagnostic tools to detect diabetes earlier and prevent disease progression. This review was conducted to determine what is known from the literature about the effect of EV crosstalk on pancreatic β-cell function and viability in the pathogenesis of diabetes mellitus, to perform a gap analysis for future research directions, and to discuss implications of available evidence for diabetes care. The literature search yielded 380 studies from which 31 studies were determined to meet eligibility criteria. The majority of studies had the disease context of autoimmunity in T1DM. The most commonly studied EV crosstalk dynamics involved localized EV-mediated communication between β-cells and other islet cells, or between β-cells and immune cells. Other organs and tissues secreting EVs that affect β-cells include skeletal muscle, hepatocytes, adipocytes, immune cells, bone marrow, vascular endothelium, and mesenchymal stem cells. Characterization of EV cargo molecules with regulatory effects in β-cells was conducted in 24 studies, with primary focus on microRNA cargo. Gaps identified included scarcity of evidence for the effect on β-cell function and viability of EVs from major metabolic organs/tissues such as muscle, liver, and adipose depots. Future research should address these gaps as well as characterize a broader range of EV cargo molecules and their activity in β-cells.

Shedding Light on the Role of Extracellular Vesicles in HIV Infection and Wound Healing.

Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research has documented that EVs, specifically exosomes and MVs, play an important role in HIV infection, either by promoting HIV infection and pathogenesis or by inhibiting HIV-1 to a certain extent. We have also previously reported that EVs (particularly exosomes) from vaginal fluids inhibit HIV at the post-entry step (i.e., reverse transcription, integration). Besides the role that EVs play in HIV, they are also known to regulate the process of wound healing by regulating both the immune and inflammatory responses. It is noted that during the advanced stages of HIV infection, patients are at greater risk of wound-healing and wound-related complications. Despite ongoing research, the data on the actual effects of EVs in HIV infection and wound healing are still premature. This review aimed to update the current knowledge about the roles of EVs in regulating HIV pathogenesis and wound healing. Additionally, we highlighted several avenues of EV involvement in the process of wound healing, including coagulation, inflammation, proliferation, and extracellular matrix remodeling. Understanding the role of EVs in HIV infection and wound healing could significantly contribute to the development of new and potent antiviral therapeutic strategies and approaches to resolve impaired wounds in HIV patients.

Immortalised Hippocampal Astrocytes from 3xTG-AD Mice Fail to Support BBB Integrity In Vitro: Role of Extracellular Vesicles in Glial-Endothelial Communication.

Impairments of the blood-brain barrier (BBB) and vascular dysfunction contribute to Alzheimer's disease (AD) from the earliest stages. However, theinfluence of AD-affected astrocytes on the BBB remain largely unexplored. In the present study, we created an in vitro BBB using human-immortalized endothelial cells in combination with immortalized astroglial cell lines from the hippocampus of 3xTG-AD and wild-type mice (3Tg-iAstro and WT-iAstro, respectively). We found that co-culturing endothelial monolayers with WT-iAstro upregulates expression of endothelial tight junction proteins (claudin-5, occludin, ZO-1) and increases the trans-endothelial electrical resistance (TEER). In contrast, co-culturing with 3Tg-iAstro does not affect expression of tight junction proteins and does not change the TEER of endothelial monolayers. The same in vitro model has been used to evaluate the effects of extracellular vesicles (EVs) derived from the WT-iAstro and 3Tg-iAstro. The EVs derived from WT-iAstro increased TEER and upregulated expression of tight junction proteins, whereas EVs from 3Tg-iAstro were ineffective. In conclusion, we show for the first time that immortalized hippocampal astrocytes from 3xTG-AD mice exhibit impaired capacity to support BBB integrity in vitro through paracrine mechanisms and may represent an important factor underlying vascular abnormalities during development of AD.

The Role of Extracellular Vesicles as Allies of HIV, HCV and SARS Viruses.

Extracellular vesicles (EVs) are lipid bilayer-enclosed entities containing proteins and nucleic acids that mediate intercellular communication, in both physiological and pathological conditions. EVs resemble enveloped viruses in both structural and functional aspects. In full analogy with viral biogenesis, some of these vesicles are generated inside cells and, once released into the extracellular milieu, are called “exosomes”. Others bud from the plasma membrane and are generally referred to as “microvesicles”. In this review, we will discuss the state of the art of the current studies on the relationship between EVs and viruses and their involvement in three important viral infections caused by HIV, HCV and Severe Acute Respiratory Syndrome (SARS) viruses. HIV and HCV are two well-known pathogens that hijack EVs content and release to create a suitable environment for viral infection. SARS viruses are a new entry in the world of EVs studies, but are equally important in this historical framework. A thorough knowledge of the involvement of the EVs in viral infections could be helpful for the development of new therapeutic strategies to counteract different pathogens.

The role of extracellular vesicles from stored RBC units in B lymphocyte survival and plasma cell differentiation.

Extracellular vesicles (EVs) are small, double-membrane vesicles derived from erythrocytes, leukocytes, platelets, and cells of multiple tissues under physiologic or pathologic conditions. The role of EVs in stored RBC units is of great interest with respect to transfusion-related immunomodulation. The current study focuses on the quantity of EVs isolated from stored RBC units and their action on Bcell-mediated immune responses. The in vitro experiment demonstrated that EVs exhibited a negative role in Bcell survival, plasmacytic differentiation, and class switch recombination under LPS stimulation. Furthermore, LPS-induced antibody production was significantly decreased after EVs injection in vivo. Biochemical analysis revealed that EVs hampered the expression of Blimp-1 and IRF4 and the activation of NF-κB pathway in LPS-primed Bcells. Overall, these data imply a vital role for EVs isolated from RBC units in Bcell-mediated immune responses.

Thyroid tumor cells-fibroblasts crosstalk: role of extracellular vesicles.

Tumor-stroma crosstalk leads to a tumor-promoting microenvironment. In this milieu, extracellular vesicles (EVs) are protagonists in cell-cell communication. Despite thyroid cancer being the most common endocrine malignancy, the contribution of the tumor microenvironment to thyroid cancer progression is still largely underexplored. We focused on the role of thyroid tumor cell-fibroblast interaction and EVs as mediators of tumor-stroma interplay, in the promotion of thyroid tumor aggressiveness. Thyroid tumor (TPC-1, 8505c) or non-tumor thyroid cells (NThyOri) were co-cultured with human fibroblasts (Fb). Thyroid cell migration was investigated by the wound-healing assay and actin-network staining. Cell-CD147 expression was characterized by flow cytometry. EVs, obtained by ultracentrifugation of conditioned media (CMs), were characterized by transmission electron-microscopy and CD81 and CD147 expression. Metalloproteinases (MMPs) were evaluated by zymography in CMs. A migratory phenotype was triggered in thyroid tumor cells treated with CMs from Fb or from Fb-thyroid tumor cell co-cultures. Fb-thyroid cell co-cultures induced the secretion of proMMP9 and proMMP2 and led to a significant MMP2 activation in CMs. Fb, thyroid cells and Fb-thyroid cell co-cultures released EVs, and remarkably, EVs released by Fb-thyroid tumor cell co-cultures induced the secretion of proMMP2 and the expression of MMP2 from normal Fb. A significant CD147 expression was demonstrated in Fb-thyroid tumor cell-derived EVs. These findings reveal the role of Fb and thyroid tumor cell-Fb interaction in the promotion of a microenvironment suitable for thyroid tumor progression. Moreover, they highlight, for the first time, the role of thyroid tumor cell-Fb interaction in the production of specialized EVs.

The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance

Extracellular vesicles (EVs) mediate intercellular signaling and communication, allowing the intercellular exchange of proteins, lipids, and genetic material. Their recognized role in the maintenance of the physiological balance and homeostasis seems to be severely disturbed throughout the carcinogenesis process. Indeed, the modus operandi of cancer implies the highjack of the EV signaling network to support tumor progression in many (if not all) human tumor malignancies. We have reviewed the current evidence for the role of EVs in affecting cancer hallmark traits by: (i) promoting cell proliferation and escape from apoptosis, (ii) sustaining angiogenesis, (iii) contributing to cancer cell invasion and metastasis, (iv) reprogramming energy metabolism, (v) transferring mutations, and (vi) modulating the tumor microenvironment (TME) by evading immune response and promoting inflammation. Special emphasis was given to the role of EVs in the transfer of drug resistant traits and to the EV cargo responsible for this transfer, both between cancer cells or between the microenvironment and tumor cells. Finally, we reviewed evidence for the increased release of EVs by drug resistant cells. A timely and comprehensive understanding of how tumor EVs facilitate tumor initiation, progression, metastasis and drug resistance is instrumental for the development of innovative EV-based therapeutic approaches for cancer.

The role of extracellular vesicles in prostate cancer with clinical applications.

In mammalian cells, extracellular vesicles (EVs) derived from the endosomal system carry many different kinds of bioactive molecule to deliver to recipient cells in a paracrine or endocrine manner. EVs can mediate local and systemic intercellular communications, including reeducating stromal cells, remodeling the architecture of the tumor microenvironment, modulating cancer metabolism and metastases, or even conferring drug resistance. Because the molecular and functional characteristics of prostate cancer (PCa) evolve over time, the bioactive molecule profiles/signatures of tumor-derived EVs (TDEs) reflect the real-time status of cancer cells. TDEs appear to be valuable diagnostic and prognostic biomarkers as well as potential therapeutic vehicles, suggesting their essential role in precision medicine of disease management. We summarized critical aspects of TDEs in PCa and discussed their potential clinical applications.

The Osteosarcoma Microenvironment: A Complex But Targetable Ecosystem.

Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.

Transfection of maternal cells with placental extracellular vesicles in preeclampsia

The role of extracellular vesicles is widely studied. As well as other organs, placenta produces extracellular vesicles during both, normal and pathological pregnancies. During pregnancy, placental/fetal free DNA circulates in maternal blood. Concentrations of free placental DNA are much higher when pregnancy complications of various etiologies occur. Such a complication could be preeclampsia. In our previous animal model, administration of pure DNA isolated from fetus did not induce any prenatal complications. Here we hypothesize that in real life during preeclampsia or other pregnancy complications, placental DNA might be transported by extracellular vesicles to maternal cells. Also, our preliminary data prove that placental DNA is present in circulating exosomes in maternal blood. Therefore, a lipid bilayer of extracellular vesicles could protect DNA from degradation by enzymes. Extracellular vesicles tend to merge with other cells, therefore, following expression of fetal genes from placental extracellular vesicles in maternal cells could lead to an immune response already observed in pregnancy complications. Future studies should be mainly focused on verification of our hypothesis and evaluate the potential of placental/fetal extracellular vesicles and their gene transfer in preeclampsia or other pregnancy complications.