To date, extracellular vesicles (EVs) have been extensively investigated as potential substitutes for cell therapy. Research has suggested their ability to overcome serious risks associated with the application of these cells. Although, the translation of EVs into clinical practice is hampered by the lack of a cheap reasonable way to obtain a clinically relevant number of EVs, an available method for the large-scale production of EVs ensures vesicles’ integrity, preserves their biological activity, and ensures they are well reproducible, providing homogeneity of the product from batch to batch. In this review, advances in the development of methods to increase EVs production are discussed. The existing approaches can be divided into the following: (1) those based on increasing the production of natural EVs by creating and using high capacity “cell factories”, (2) those based on the induction of EVs secretion under various cell stressors, and (3) those based on cell fragmentation with the creation of biomimetic vesicles. The aim of this review is to stimulate the introduction of EVs into clinical practice and to draw attention to the development of new methods of EVs production on a large scale.

Extracellular vesicles (EVs) are nanosized lipid bilayer vesicles that are released by almost all cell types. They range in diameter from 30 nm to several micrometres and have the ability to carry biologically active molecules such as proteins, lipids, RNA, and DNA. EVs are natural vectors and play an important role in many physiological and pathological processes. The amount and composition of EVs in human biological fluids serve as biomarkers and are used for diagnosing diseases and monitoring the effectiveness of treatment. EVs are promising for use as therapeutic agents and as natural vectors for drug delivery. However, the successful use of EVs in clinical practice requires an understanding of their biodistribution in an organism. Numerous studies conducted so far on the biodistribution of EVs show that, after intravenous administration, EVs are mostly localized in organs rich in blood vessels and organs associated with the reticuloendothelial system, such as the liver, lungs, spleen, and kidneys. In order to improve resolution, new dyes and labels are being developed and detection methods are being optimized. In this work, we review all available modern methods and approaches used to assess the biodistribution of EVs, as well as discuss their advantages and limitations.

The immunosuppressive potential of mesenchymal stem cells has been extensively investigated in many studies in vivo and in vitro. In recent years, a variety preclinical and clinical studies have demonstrated that mesenchymal stem cells ameliorate immune-mediated disorders, including autoimmune diseases. However, to date mesenchymal stem cells have not become a widely used therapeutic agent due to safety challenges, high cost and difficulties in providing long term production. A key mechanism underpinning the immunomodulatory effect of MSCs is the production of paracrine factors including growth factors, cytokines, chemokines, and extracellular vesicles (EVs). MSCs derived EVs have become an attractive therapeutic agent for immunomodulation and treatment of immune-mediated disorders. In addition to many preclinical studies of MSCs derived EVs, their beneficial effects have been observed in patients with both acute graft-vs.-host disease and chronic kidney disease. In this review, we discuss the current findings in the field of MSCs derived EVs-based therapies in immune-mediated disorders and approaches to scale EV production for clinical use.

The phenomenon of mitochondria donation is found in various tissues of humans and animals and is attracting increasing attention. To date, numerous studies have described the transfer of mitochondria from stem cells to injured cells, leading to increased ATP production, restoration of mitochondria function, and rescue of recipient cells from apoptosis. Mitochondria transplantation is considered as a novel therapeutic approach for the treatment of mitochondrial diseases and mitochondrial function deficiency. Mitochondrial dysfunction affects cells with high energy needs such as neural, skeletal muscle, heart, and liver cells and plays a crucial role in type 2 diabetes, as well as Parkinson’s, Alzheimer’s diseases, ischemia, stroke, cancer, and age-related disorders. In this review, we summarize recent findings in the field of mitochondria donation and mechanism of mitochondria transfer between cells. We review the existing clinical trials and discuss advantages and disadvantages of mitochondrial transplantation strategies based on the injection of stem cells, isolated functional mitochondria, or EVs containing mitochondria.

Cancer is a heterogeneous disease. Each individual tumor is unique and characterized by structural, cellular, genetic and molecular features. Therefore, patient-derived cancer models are indispensable tools in cancer research and have been actively introduced into the healthcare system. For instance, patient-derived models provide a good reproducibility of susceptibility and resistance of cancer cells against drugs, allowing personalized therapy for patients. In this article, we review the advantages and disadvantages of the following patient-derived models of cancer: (1) PDC—patient-derived cell culture, (2) PDS—patient-derived spheroids and PDO—patient-derived organoids, (3) PDTSC—patient-derived tissue slice cultures, (4) PDX—patient-derived xenografts, humanized PDX, as well as PDXC—PDX-derived cell cultures and PDXO—PDX-derived organoids. We also provide an overview of current clinical investigations and new developments in the area of patient-derived cancer models. Moreover, attention is paid to databases of patient-derived cancer models, which are collected in specialized repositories. We believe that the widespread use of patient-derived cancer models will improve our knowledge in cancer cell biology and contribute to the development of more effective personalized cancer treatment strategies.

Extracellular vesicles (EVs) are membrane vesicles released by cells into the extracellular space. EVs mediate cell-to-cell communication through local and systemic transportation of biomolecules such as DNA, RNA, transcription factors, cytokines, chemokines, enzymes, lipids, and organelles within the human body. EVs gained a particular interest from cancer biology scientists because of their role in the modulation of the tumor microenvironment through delivering bioactive molecules. In this respect, EVs represent an attractive therapeutic target and a means for drug delivery. The advantages of EVs include their biocompatibility, small size, and low immunogenicity. However, there are several limitations that restrict the widespread use of EVs in therapy, namely, their low specificity and payload capacity. Thus, in order to enhance the therapeutic efficacy and delivery specificity, the surface and composition of extracellular vesicles should be modified accordingly. In this review, we describe various approaches to engineering EVs, and further discuss their advantages and disadvantages to promote the application of EVs in clinical practice.