Safety and Regenerative Properties of Immortalized Human Mesenchymal Stromal Cell Secretome
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 <i>TERT</i> 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.
Authors
- Vladimir Popov (ORCID: https://orcid.org/0000-0002-5039-7152)
- Anna Monakova (ORCID: https://orcid.org/0000-0002-7123-6374)
- M. A. Vigovskiy (ORCID: https://orcid.org/0000-0003-2103-8158)
- Zhanna Akopyan (ORCID: https://orcid.org/0000-0002-0989-7825)
- Anastasia Efimenko (ORCID: https://orcid.org/0000-0002-0696-1369)
- Konstantin Kulebyakin (ORCID: https://orcid.org/0000-0001-6954-5787)
- Olga Grigorieva (ORCID: https://orcid.org/0000-0003-2954-2420)
- Tkachuk Va (ORCID: https://orcid.org/0000-0002-7492-747X)
- Vadim Chechekhin (ORCID: https://orcid.org/0000-0001-8489-9954)
- Elena Shagimardanova (ORCID: https://orcid.org/0000-0003-2339-261X)
- Maria Kulebyakina (ORCID: https://orcid.org/0000-0001-5956-1265)
- Uliana Dyachkova (ORCID: https://orcid.org/0000-0002-6119-8976)
- Nataliya Basalova (ORCID: https://orcid.org/0000-0002-2597-8879)
- Джауари Сталик Станиславович (ORCID: https://orcid.org/0000-0001-5480-2322)
- Alexandra L. Primak (ORCID: https://orcid.org/0000-0002-1386-5922)
- Guzel R. Gazizova (ORCID: https://orcid.org/0000-0003-4978-8495)
- Maxim N. Karagyaur (ORCID: https://orcid.org/0000-0003-4289-3428)
- Veronika Sysoeva (ORCID: https://orcid.org/0000-0001-9885-9056)
- В. И. Турилова (ORCID: https://orcid.org/0000-0002-6318-9395)
- Natalia Kalinina (ORCID: https://orcid.org/0000-0003-3497-9619)
- Kirill Bozov (ORCID: https://orcid.org/0009-0006-8442-8582)
- Anastasia Tolstoluzhinskaya (ORCID: https://orcid.org/0000-0001-8362-2902)
- Elizaveta Chechekhina (ORCID: https://orcid.org/0000-0002-5377-2712)
- Mariya Skryabina (ORCID: https://orcid.org/0000-0003-3128-2699)
- T.V. Yakovleva (ORCID: https://orcid.org/0000-0002-4772-5645)
Institutions
- Skolkovo Institute of Science and Technology (RU)
- Kazan Federal University (RU)
- Institute of Cytology (RU)
- Moscow State University (TJ)
- Thermo Fisher Scientific (Norway) (NO)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-09-24
- DOI
- https://doi.org/10.3390/ijms26199322
- Primary Topic
- Mesenchymal stem cell research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Lomonosov Moscow State University