TRPS-Driven Discoveries: From Bone Regeneration to Cardiac Disease Biomarkers

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A wrap-up of publications featuring Tunable Resistive Pulse Sensing technology in Q4 of 2023.

1) Could therapeutic EVs enhance bone regeneration?

Given the painful and disruptive nature of bone fractures, bone-healing interventions are of great clinical interest. Following the success of mRNA-based therapeutics over the past few years, Ma et al. (2023) explored the therapeutic potential of EVs in a bone tissue regeneration setting.1 Using TM-nanoEP, a commercially available system, the group produced EVs endogenously loaded with a plasmid cocktail of VEGF-A and BMP-2 mRNAs.

The therapeutic EVs were applied in a rat model, with angiogenic and osteogenic activity reported to be better than that of a synthetic lipid nanoparticle formulation, as indicated by RNA-seq and RT-qPCR analysis, tube formation assays, and measures of alkaline phosphatase activity. Enhanced expression of certain EV miRNAs was also noted and said to have a synergistic effect. EVs were isolated using qEV isolation, with particle concentration and particle size distribution measured across the different purified collection volumes using Tunable Resistive Pulse Sensing. In this proof-of-concept study, the authors also describe the use of an injectable, hydrogel ‘cage’ for preserving EV integrity and cargo prior to implantation.

2) A potential EV biomarker for chemotherapy-induced heart disease

Despite the many advancements in cancer treatment, life on the other side of chemotherapy comes with its own health challenges. Among them is the possibility of late-onset cardiomyopathy, particularly for those who have received doxorubicin (DOXO) treatment. In a study by Yarana et al. (2023), the Exoid was used to measure the size and concentration of EVs, which were assessed for their biomarker utility in this context.2 Specifically, the focus was on EVs containing a protein called 4HNE-adducted protein: one that plays a role in DOXO-induced cardiotoxicity and is linked to a variety of cardiovascular disorders. Using a rodent model, Yarana et al. (2023) made a number of interesting connections that position 4HNE-adducted protein in EVs as a biomarker candidate. Of note, changes in the levels of 4HNE-adducted protein in EVs were apparent 9 days after DOXO treatment, whereas altered NTproBNP levels (an established indicator of clinical heart failure) were not yet apparent at the same point.

3) Serum EVs explored for predicting survival of intrahepatic cholangiocarcinoma (iCCA)

In a study published in hepatology journal JHEP Reports, Louis et al. describe the presence and dynamics of a novel, clinically relevant EV-based biomarker associated with intrahepatic cholangiocarcinoma (iCCA), an aggressive liver cancer.3 CircLTBP2 is a circular RNA recognised for its pro-metastatic activity, according to studies of human iCCA cell lines. In this study, expression of this biomarker candidate predicted a reduced survival, as detected in both tumour tissues and in serum EVs from patients with iCCA. As part of the characterisation process, EV size distribution was characterised using Tunable Resistive Pulse Sensing. While the study provides proof of concept, ultracentrifugation was the EV isolation method of choice – a notoriously labour-intensive approach prone to variability. Of note, a shift to a larger-scale study of EVs would require a shift to a more scalable EV isolation method.

4) How EVs from throat cancer induce dendritic cell response

It is known that small EVs derived from nasopharyngeal carcinoma have an immunosuppressive effect on the tumour microenvironment – and Lefebvre et al. 2023 set out to find out how.4 In a study published in the Journal of Extracellular Vesicles, the group describe new insights which point towards vesicular Galectin-9 (Gal9) as playing a key role in the recruitment of mature dendritic cells – cells that had been demonstrated as being effective at inhibiting T cell proliferation. Gal9 is a lectin (a carbohydrate-binding protein) with ambiguous and debated roles in cancer, as it has been associated with both poor and good cancer prognosis in different studies. Small EVs were characterised using a range of methods including the Exoid for particle size distribution and concentration.

Ready for high-resolution particle analysis? Learn all about the Exoid here.


  1. Ma, Y. et al. Exosomal mRNAs for Angiogenic–Osteogenic Coupled Bone Repair. Advanced Science 10, (2023). Doi:10.1002/advs.202302622
  2. Yarana, C. et al. Potential roles of 4HNE-adducted protein in serum extracellular vesicles as an early indicator of oxidative response against doxorubicin-induced cardiomyopathy in rats. Current Research in Toxicology 5, 100134 (2023). Doi:10.1016/j.crtox.2023.100134
  3. Louis, C. et al. TGFβ-induced circLTBP2 predicts a poor prognosis in intrahepatic cholangiocarcinoma and mediates gemcitabine resistance by sponging miR-338-3p. JHEP Reports 5, 100900–100900 (2023). Doi:10.1016/j.jhepr.2023.100900
  4. Lefebvre, A. et al. Extracellular vesicles derived from nasopharyngeal carcinoma induce the emergence of mature regulatory dendritic cells using a galectin‐9 dependent mechanism. Journal of Extracellular Vesicles 12, 12390 (2023). Doi:10.1002/jev2.12390

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