Safety and Regenerative Properties of Immortalized Human Mesenchymal Stromal Cell Secretome

TL;DR

This study shows that immortalized human mesenchymal stromal cells can produce a safe and effective secretome for regenerative therapy without losing their original properties.

Contribution

The study demonstrates that TERT-immortalized MSCs produce a safe and consistent secretome suitable for large-scale clinical applications.

Findings

MSC immortalization via TERT overexpression does not alter secretome composition or activity.

Secretome of immortalized MSCs lacks telomerase and transforming activity.

Immortalized MSCs can serve as a reliable source for standardized secretome production.

Abstract

The secretome of mesenchymal stromal cells (MSCs) can efficiently stimulate regeneration and therefore is a tempting remedy for “cell-free cellular therapy”. However, the usage of primary MSC cultures as secretome producers for translation studies has obvious obstacles, including the rapid aging of MSC cultures, the need for a large number of verified donors, and donor-to-donor variability of secretome content. MSCs immortalization makes it possible to overcome those limitations and to obtain secretome-producing cultures with a prolonged lifetime. However, the efficacy and safety of such secretomes are critical issues that limit their usage as therapeutic agents. In this study, we tested in large detail how the immortalization of MSC cultures affects the content, biological activity and safety of their secretome. MSCs immortalization via the overexpression of human TERT gene does not significantly alter the qualitative and quantitative composition of their secretome or its activity according to the results of proteomic analysis, ELISA, qPCR and functional tests in vitro. Moreover, we have demonstrated that the secretome of immortalized MSCs does not contain detectable amounts of telomerase and does not possess any transforming activity. Altogether, our data suggest that immortalized MSC cultures may become a reliable source for obtaining standardized active secretome in large-scale quantities for clinical use.

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