On the Choice of the Extracellular Vesicles for Therapeutic Purposes

Abstract

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of disease biomarkers and have high potential benefits in regenerative medicine. Indeed, they deliver both chemical and bio-molecules in a way that within exosomes drugs are more effective that in their exosome-free form. Thus, to date, we know that exosomes are shuttle disease biomarkers and probably the most effective way to deliver therapeutic molecules within target cells. However, we do not know exactly which exosomes may be used in therapy in avoiding side effects as well. In regenerative medicine, it will be ideal to use autologous exosomes, but it seems not ideal to use plasma-derived exosomes, as they may contain potentially dangerous molecules. Here, we want to present and discuss a contradictory relatively unmet issue that is the lack of a general agreement on the choice for the source of extracellular vesicles for therapeutic use.

Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?

“…Given the importance of the sequential expression of HSPs in stressed BMECs and in the differentiation of NSCs/NPCs, it will be essential to show which HSPs contribute to functional neurons, astrocytes, or oligodendrocytes, capable of repairing lesions in the adult brain or of inducing cerebral angiogenesis (144). The answer to these questions will be beneficial for the implementation of new therapeutic concepts based on biomaterials and the use of HSPs in the treatment of cerebrovascular diseases, brain trauma, neurodegeneration, brain tumors, or neuroinfection (15, 145, 146).…”

Carbonic anhydrase IX as a novel candidate in liquid biopsy

“…Extracellular Vesicles (EVs) are lipid structures released from cells. EVs contain proteins and nucleic acids and play a role in cellular communication, immune regulation, and microenvironmental modulation 73,74 . Nanosized exosomes (70-150 nm) are the most prominent members of these so-called extracellular vesicles (EVs) and are released from body fluids such as urine, ascites, and plasma 73,74 .…”

“…EVs contain proteins and nucleic acids and play a role in cellular communication, immune regulation, and microenvironmental modulation 73,74 . Nanosized exosomes (70-150 nm) are the most prominent members of these so-called extracellular vesicles (EVs) and are released from body fluids such as urine, ascites, and plasma 73,74 . Moreover, they are liberated over all kinds of body cells (epithelium cells, haematopoietic cells, adipocytes, healthy and malignant cells) 75 , released in almost all cell types under physiological and pathophysiological conditions and mediate intercellular contacts 76 .…”

“…Moreover, they are liberated over all kinds of body cells (epithelium cells, haematopoietic cells, adipocytes, healthy and malignant cells) 75 , released in almost all cell types under physiological and pathophysiological conditions and mediate intercellular contacts 76 . A theranostic solution could be represented by the nanosized EVs, which may transmit biomarkers of diseases and/or vectors of therapeutic molecules, offering a unique opportunity to use a combination of different markers specifically expressed for tumour-derived EVs 74,76,77 . For example, Prostate-Specific Antigen (PSA) does not differentiate between benign prostatic hyperplasia (BPH) and a Prostate Cancer (PC), resulting in large numbers of unnecessary biopsies and missed diagnosis of cancer.…”

Secretome of Adipose Tissue-Derived Stem Cells (ASCs) as a Novel Trend in Chronic Non-Healing Wounds: An Overview of Experimental In Vitro and In Vivo Studies and Methodological Variables

“…In this scenario, the study of ASC-conditioned medium (ASC-CM) (also known as ASC-secretome) has opened the way for the development of new cell-free therapies for tissue repair and regeneration [43][44][45][46][47][48]. Like total secretome, its vesicular fraction (the so-called extracellular vesicles, EVs), able to transfer active cargoes between the cells, is thought to exert biological activity similar to ASCs, thus representing another promising novel therapy against non-healing wounds [38,[49][50][51].…”