#extracellular vesicles

An 'extra-large extracellular vesicle' (XLEV), far bigger than an exosome, is released from the region around the cell nucleus loaded with sonic hedgehog, the molecule that shapes the body. The work comes from the University of Tokyo. The surprise was that what pushed that release was the 'off' form of a protein called Rab18 — a logic that contrasts with conventional models, which have emphasized the GTP-bound form.

An original research paper that ran human bone marrow–derived MSCs continuously in a hollow fiber bioreactor for about 40 days and kept harvesting the small extracellular vesicles (sEVs) that came out, four times a week. The paper reports that particle size, markers, and yield were stable (no numerical value for particle size appears in the main text), while mass spectrometry found 1,618 proteins differentially altered between Phase 3 and Phase 1. It is entirely a story from inside a culture device, and whether the later vesicles work was never measured once.

IL-10, the cytokine that calms inflammation, never quite became a drug: it is unstable and clears from the body fast. A Michigan State University team harvested extracellular vesicles from cells made to overexpress IL-10 with minicircle DNA, and shows they are more stable than recombinant IL-10 and quiet inflammatory macrophages. But naïve vesicles, with no IL-10 gene introduced, worked too. Every experiment is in cultured cells.

As obesity drags on, pancreatic beta cells multiply and work harder to hold off diabetes (beta cell compensation). A team at China Pharmaceutical University shows that in this emergency, beta cells release extracellular vesicles (sEV) loaded with miR-151 and turn nearby mesenchymal stem cells (MSC) into helpers. Freed from the KLF9 brake, the MSCs proliferate and secrete WNT to support beta cells. Dr. Exotaro unpacks this cell-and-mouse preclinical study.

MSC-derived extracellular vesicles are biocompatible, low-immunogenicity 'natural nanocapsules.' This review maps six strategies to engineer them into drug carriers and their clinical safety data.