Biological properties of extracellular vesicles

Extracellular vesicles (EVs) are small membrane structures released by cells and have attracted attention in recent years. They are diverse in size, origin, content, and function, making their biological properties highly complex. The following is an overview of the biological properties of extracellular vesicles:

Extracellular vesicles are classified into exosomes, microvesicles, and apoptotic bodies based on their size and origin. Exosomes are generated from intracellular structures called endosomes and are approximately 30-150nm in size. On the other hand, microvesicles are directly shed from the cell membrane and are larger than exosomes, ranging from 100-1000nm. Apoptotic bodies are released during programmed cell death (apoptosis) and are even larger, with a size of 1-5µm.

These extracellular vesicles serve as a means of communication between cells. They can transport various molecules such as proteins, lipids, RNA (mRNA, miRNA, etc.), and DNA. These molecules are delivered to target cells by the vesicles and exert their functions there. For example, miRNAs contained in the vesicles can control gene expression in target cells.

Furthermore, extracellular vesicles are released not only from healthy cells but also from diseased cells such as cancer cells and virus-infected cells. These vesicles have the potential to provide insights for diagnosing conditions, predicting prognosis, and developing new therapies.

Extracellular vesicles act as “packages” in which cells wrap part of themselves and send to other cells, carrying biological information. These vesicles contain diverse biomolecules such as RNA, proteins, and lipids that reflect the type and state of their originating cells.

Diagnosis of conditions: Extracellular vesicles reflect the state of the cells from which they originate. For example, cancer cells release extracellular vesicles with distinct characteristics compared to normal cells. Analyzing these characteristics can help determine the presence, type, and stage of cancer. Analysis of extracellular vesicles present in body fluids such as blood and urine is also being pursued for the development of non-invasive diagnostic methods (liquid biopsy).

Specific examples of using extracellular vesicles for condition diagnosis include early detection and identification of cancer types.

For example, in lung cancer, exosomes derived from lung cancer cells (a type of extracellular vesicle) have been found to be present in the bloodstream. These exosomes contain RNA and proteins specific to lung cancer cells, enabling the diagnosis of lung cancer.

Specific literature references for lung cancer diagnosis:

Sandfeld-Paulsen, B., Aggerholm-Pedersen, N., Baek, R., Jakobsen, K. R., Meldgaard, P., Folkersen, B. H., … & Sorensen, B. S. (2016). Exosomal proteins as prognostic biomarkers in non-small cell lung cancer. Molecular oncology, 10(10), 1595-1602.
Research is also underway on using exosomes derived from prostate cancer cells for prostate cancer diagnosis. By combining them with known markers such as prostate-specific antigen (PSA), more accurate diagnosis is expected.

Specific literature references for prostate cancer diagnosis:

Huang, X., Yuan, T., Liang, M., Du, M., Xia, S., Dittmar, R., … & Marks, J. R. (2015). Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. European urology, 67(1), 33-41.

Prognosis assessment: Extracellular vesicles are also useful for evaluating disease progression and treatment efficacy. For example, assessing the effectiveness of cancer treatment usually requires imaging diagnostics and tissue examinations, which are time-consuming and labor-intensive. However, analyzing extracellular vesicles allows for rapid and repetitive evaluations.

Specific example of using extracellular vesicles for prognosis assessment is prognosis prediction in cancer.

Breast cancer: The pattern of microRNA (miRNA) contained in exosomes has been shown to be a reliable biomarker for predicting the prognosis of breast cancer. Some miRNAs are closely associated with the progression of breast cancer, and their detection enables the prediction of breast cancer prognosis.

Specific literature reference for breast cancer prognosis:

Hannafon, B. N., Trigoso, Y. D., Calloway, C. L., Zhao, Y. D., Lum, D. H., Welm, A. L., … & Ding, W. Q. (2016). Plasma exosome microRNAs are indicative of breast cancer. Breast cancer research, 18(1), 90.

Lung cancer: The quantity of exosomes present in the blood of lung cancer patients has been reported to be associated with the prognosis of lung cancer. Patients with a higher quantity of exosomes in their blood tend to have a poorer prognosis.

Specific literature reference for lung cancer prognosis:

Jakobsen, K. R., Paulsen, B. S., Bæk, R., Varming, K., Sorensen, B. S., & Jørgensen, M. M. (2015). Exosomal proteins as potential diagnostic markers in advanced non–small cell lung carcinoma. Journal of extracellular vesicles, 4(1), 26659.

Development of new therapies: Extracellular vesicles not only carry their own information but also have the ability to alter the function of recipient cells upon receiving the information. This is being utilized to develop “biological delivery systems” that can deliver drugs or genes to specific cells or tissues. Additionally, the development of new immunotherapies utilizing extracellular vesicles that regulate immune responses is also expected.

For example, the use of MSC-derived exosomes for the treatment of spinal cord injuries.

Extracellular vesicles have the potential to provide hints for diagnosing conditions, predicting prognosis, and developing new therapies due to their diverse properties and functions.

However, research on extracellular vesicles is still in its early stages, and much remains to be elucidated. There are still many unresolved issues, such as the precise mechanisms of vesicle generation, the mechanisms of intercellular information transfer, the types of molecules contained within the vesicles and their selection mechanisms, as well as the distribution and functions of extracellular vesicles in the body.

Research on extracellular vesicles is expected to have a significant impact not only in life sciences but also in the fields of diagnostics, medicine, pharmacy, as well as engineering and information science. For example, extracellular vesicles released by cancer cells are known to play important roles in cancer progression and metastasis. Understanding the characteristics of extracellular vesicles released by cancer cells may lead to early detection of cancer, prevention of metastasis, and the development of new therapies. Furthermore, the development of new therapeutic techniques that utilize extracellular vesicles as “vehicles” to deliver drugs to specific tissues or cells is also being pursued.

Despite the challenges, research on extracellular vesicles is rapidly advancing. This field is filled with new discoveries and technological innovations, including the development of new isolation and purification methods, the development of new techniques to identify the contents and originating cells of vesicles, and the development of new medical technologies utilizing the functions of extracellular vesicles. It is an exciting area of research with great potential for future applications.