**1. Introduction**

The great success of the double helix molecular model of DNA [1] has been based mostly on revealing specific, chemical mechanisms. This model has enabled profound advances in technology; however, it has not completely revealed the causes of common and debilitating physiological and pathophysiological mechanisms. However, the dynamics of the genetic material depend on its interaction with membranous systems which has hitherto not been given adequate attention. Moreover, nanostructures composed of- and enclosed by- biological membranes (e.g., vesicles and nanotubes) were long overlooked [2] due to their small size and fragility. Recently,

submicron-sized membrane-enclosed cellular vesicles (CVs) that have been formed in a process in which membrane plays a key role have become a subject of increasing attention. By being released into the cell exterior, they can move more or less freely in the surrounding medium. Extensive studies and empirical knowledge indicate that these tiny particles may have a great impact on living systems, in particular, because they present an intercellular communication system that connects different kingdoms of life. CVs include microexovesicles, exosomes, enveloped viruses, and cellular membrane endovesicles.

The structure of a membrane-enclosed entity that carries a specific cargo presents a foundation stone of life and dwells also on its border. Namely, the physical properties of membrane-enclosed entities are shared with any small particles that attain their configuration according to the minimal energy of the system (referred here as colloid systems). While consideration of biological nanostructures needs the support of a rigorous physical description, new evidence regarding nanoscale features needs interpretation by the development of new physical models, specific to these materials. We believe that the research of nanoscale systems at the cellular level requires the intertwining of existing fields of physics, chemistry, biology, and medicine in the course of their growth. By addressing the physical properties, methods of theoretical physics can be used to describe the system, interpret experimental data, and predict the behavior of the system.

In order to be studied, CVs should be harvested from their natural environment. Presently, integration of different methods is recommended [3], however, new technically advanced solutions are sought. The most commonly used method for CV harvesting involves differential centrifugation [4], which can be followed by using for example sucrose or iodixanol gradient [5]. As this technique is time-consuming and of limited access, alternative techniques were proposed. Ultrafiltration, flow field-flow fractionation, dialysis, size exclusion chromatography (SEC), microchip-based techniques, and precipitation-based methods are being developed to harvest CVs, alone or in combination with ultracentrifugation-based methods. Immunoaffinity-based isolation can also be applied to harvest CVs with particular surface protein composition [6]. Recently, a number of commercial kits are made available and have been widely reported in the literature for CV isolation. For example, ExoQuick (System Biosciences) and Total Exosome Isolation kits (TEI, Invitrogen) rely on polymer precipitation; qEV (Izon) is based on SEC; Millipore uses centrifugal filter devices for ultrafiltration; and exoEasy (Qiagen) is based on membrane affinity binding [7]. But different isolation methods were found to lead to different CV populations [8] due to mechanical and thermal stress and chemical reactions. Although the suggested methods are faster and easier to apply, a recent thorough comparison between isolates obtained from these methods and ultracentrifugation showed that ultracentrifugation is still the most appropriate method among those tested as regards purity [7].

According to their features, CVs are ideal candidates to serve as biomarkers, nanosized drug-delivery vehicles, and mediators for a variety of therapeutics in oncology, immune therapy, and regenerative medicine [9–11]. Thus, CVs have the potential for great clinical impact in nanomedicine. The dual potential of CVs as diagnostic tools and as therapeutic agents supports their use in "theranostics" [11–13]. This area of nanomedicine focuses on multidisciplinary research to set up new systems for various nanobiomedical applications, ranging from the medical use of nanoplatform-based diagnostic agents to therapeutic agents for possible future applications [14]. Furthermore, the theranostic "all-in-one approach" has great potential in the field of personalized medicine, as it enables the detection and monitoring of

*Morphology and Formation Mechanisms of Cellular Vesicles Harvested from Blood DOI: http://dx.doi.org/10.5772/intechopen.101639*

disease in individual patients, possibly in early clinical stages, as well as targeted drug delivery at the site of the disease.

In order to manipulate cellular vesicles (CVs), the process of their formation should be better understood. Vesiculation of biological membranes was studied theoretically and experimentally. CVs were isolated from different biological samples, including blood [15–20]. In phospholipid vesicles, shape transformations involving evaginations were studied [20–23]. Budding and vesiculation of erythrocytes were also considered [24–29]. While erythrocytes shed vesicles in the final stage of the membrane budding, platelets undergo fragmentation in the shear stress [30].

Visualization of the samples is a prerequisite to identify CVs in samples. As they are very small, CVs are hidden within the organisms or cell assemblies and they cannot be directly observed in their natural environment. The methods used for their harvesting, observation, and assessment are to a large extent invasive enough to transform them to such extent that identification of their original nature is obscured.

We found that a large pool of submicron-sized particles in the isolates from blood was formed during the processing of samples [31–33]. This indicates that the formation of CVs in isolates can be influenced upon by changing the parameters of processing which is of advantage for the production of therapeutic preparations from biological samples.

In this review, we would like to point to some common properties of CVs that we characterize by the key role of the membrane in shape determination and refer to as colloid CVs. Also, we will address other types of cellular particles that can be present in the samples, for example, viruses.
