Promising Extracellular Vesicles Research Updates in Functional Joint Repair and Cancer Diagnosis

The 2023 Asia Pacific Societies for Extracellular Vesicles (APSEV) Conference, organized by the Taiwan Society for Extracellular Vesicles (TSEV) and co-organized with 6 other extracellular vesicles (EV) societies in the Asia-Pacific region, was held at the National Biotechnology Research Park in Taipei, Taiwan, from March 31 to April 1. 

The in-person event was the first of its kind after the 3-year COVID-19 epidemic and brought together the best minds from Japan, Korea, Australia, New Zealand, Singapore, Taiwan, China, and Hong Kong in the field of extracellular vesicles (EV) related industries and academic research to discuss important issues of extracellular vesicles from basic science, clinical applications, and emerging trends.

Related article: Is Exosome the Next Rising Star? 

Applying MSC Exosomes in Functional Joint Repair

Day one of the APSEV Conference featured a series of plenary presentations showcasing the latest research advances in diagnostic and therapeutic applications of EVs. Professor Wei Seong Toh, Research Director of the Department of Orthopaedic Surgery of Yong Loo Lin School of Medicine at the National University of Singapore kicked off the meeting by sharing the research progress on using small EVs (including exosomes) derived from mesenchymal stromal cells (MSC) for joint and cartilage repair. 

In Prof. Toh’s presentation, he introduced a series of rat studies demonstrating the proof-of-concept of MSC exosomes for alleviating osteoarthritis, as well as promoting joint repair and bone healing, which can be achieved by restoring homeostasis of injured tissues to enable tissue repair and regeneration. As an attempt to pave the way for clinical translation, he also elucidated the underlying mechanisms of studies involving larger animal models (rabbit and pig), which test the exosome combination with hyaluronic acid and validate the safety and efficacy of MSC exosomes for functional joint repair. 

Exploring the Potential of sEVs to Improve Cancer Diagnosis

In the presentation themed “Roles of Extracellular Vesicles in Cancer Progression and Diagnostics”, Professor Andreas Möller from the Australia and New Zealand Society for Extracellular Vesicles (ANZSEV) presented data from his research team on a sensitive liquid biopsy capable of cancer screening based on the complex proteomic cargo of cancer-derived sEVs. His team also generated intriguing data on how cancer-derived EVs can specifically distribute to certain organs in the body, and increase metastatic spread which may in turn lead to poorer prognosis and lower survival rates.

Taking non-small cell lung cancer (NSCLC) as an example, Prof. Möller brought out the issue of searching for a way to identify patients at risk of disease progression or metastasis. With the findings that the exosomal content of cells at normal oxygen levels is different from those at hypoxic condition, and that a larger extent of cancer hypoxia is associated with metastasis and poor prognosis, his team proposed a minimally invasive blood test at baseline which may find out NSCLC patients with a high risk of disease progression or metastasis based on the changes in exosomal content. This blood test can be used to identify early-stage NSCLC patients who will benefit from adjuvant therapy as well as prevent overtreatment of those at higher stages. 

Microfluidic Strategy for Extracellular Vesicles

Professor Hyo-Il Jung, President of the Korean Society of Extracellular Vesicles (KSEV), presented the application of a microfluidic strategy for EVs. Conventionally, EVs like exosomes are isolated and purified from body fluids by techniques such as ultracentrifugation (UC), differential ultracentrifugation (dUC), and membrane filtration. Yet these processes are time-consuming processes, have low isolation efficiency, and are not selective to tumor-associated exosomes. Prof. Jung stated that his research laboratory has recently exploited microfluidics to overcome the above limitations. 

His team introduced a novel microfluidic chip capable of selectively separating various types of exosomes with high efficiency in a short time, depending on the expression of their surface protein. Prof. Jung described this chip as a “game changer in EV research”. Together with microfluidic devices that offer size-based, continuous and high-throughput stratification of micro-beads whose surface is coated with functional EVs (exosomes), then a rapid separation of EVs can be achieved. Thanks to this new strategy, only a small volume of biological samples is needed for the downstream analysis, and thus the device can be expected to pave the way for exosome-based early diagnosis of diseases such as various types of cancers.

Investigating sEV Uptake in Hepatocellular Carcinoma Cells

Professor Judy Yam from Li Ka Shing Faculty of Medicine at the University of Hong Kong delivered a presentation highlighting a study aiming to elucidate the uptake mechanism of sEV by hepatocellular carcinoma (HCC) cells. Previous findings from Prof. Yam’s team have demonstrated the role of HCC-derived sEVs in cancer progression and metastasis. In this study, the team focused on macropinocytosis, an sEV uptake process which they observed to occur to a greater extent in metastatic HCC cells when compared to normal liver cells and nonmetastatic HCC cells. In addition, inhibition of macropinocytosis would limit the entry of sEV and make HCC cells less aggressive.

Mechanistically, Prof. Yam’s team delineated how a high level of NHE7, a sodium-hydrogen exchanger protein regulates intracellular and endosomal pH, leading to the maturation of macropinosomes. Clinically, NHE7 is upregulated and associated with a poor prognosis of HCC. The team showed that inducible inhibition of NHE7 in established tumors would delay tumor development and suppress metastasis. 

Overall, this study provides evidence that macropinocytosis controls the uptake of sEV by HCC cells. Therefore, targeting this process and inhibiting cellular sEV uptake may be investigated as a therapeutic strategy for HCC in the future.

Author

Richard Chau