Exogenus published a study offering an indepth look at the safety profile of umbilical cord bloodderived exosomes. Exo101, a solution enriched in small extracellular vesicles produced by umbilical cord blood mononuclear cells (UCBMNCsEV), has consistently shown promisefor tissue repair. Now, we demonstrate not only Exo101’s effectiveness but also its safety.

Exosomes are generally thought to be a safe alternative to cellular therapies. These small vesicles function as important messengers in celltocell communication, by carrying signals with the capacity to modulate pathways in the recipient cells. Unlike individual molecules, which are rapidly consumed or inactivated in the vicinity of the producing cell, exosomes can travel long distances in the body while keeping their cargo intact, due to alipid bilayersimilar to cell membranes.Contrary to cells, exosomes are not living organisms, meaning they lack the capacity to replicate and form tumors. Moreover, while cells often change phenotype depending on the microenvironment, exosomes’ cargo remains stable, making their therapeutic effects more consistent. Their small size additionally confers them a safetyadvantage, namely that they are far less likely to block circulation in small vessels. All in all, exosomes are a good bet to improve the safety of cellular therapies while keeping effectiveness. Still, the exosome field lacks studies proving the predicted safety of these small,but powerful vesicles.

The work conducted by Exogenus’ team screened multiple worstcase scenarios of Exo101 administration, to evaluate any potential toxicity effects. Firstly, different primary cells and cell lines were directly exposed to high doses of Exo101 (1×10^11particles/mL). The viability or metabolic activity of peripheral blood mononuclear cells, THP1 monocytes, THP1derived macrophages,normal dermal human fibroblasts, or human umbilical vein endothelial cellswas not impacted by repeated Exo101 exposure, meaning the compound was safe under the conditions studied. In vivo, we followed the biodistribution of Exo101, which appeared to accumulate preferentially at clearance sites, such as liver, spleen, and kidneys. Intravenous injections of up to 1×10^10 total Exo101 particles, corresponding to 40times the predicted therapeutic dose, administered repeatedly over 12 weeks, had no impact on general blood cellular and biochemical parameters, nor on the morphology of major organs, specifically heart, kidney, lung, spleen, andliver.

Overall, our study shows that Exo101 has an excellent safety profile under the tested conditions and supports the assumption that exosomes are a safe alternative to cellular therapies.

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