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ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 12 - 2024 |
doi: 10.3389/fbioe.2024.1444363
Spheroid Trilineage Differentiation Model of Primary Mesenchymal Stem/Stromal Cells under Hypoxia and Serum-Free Culture Conditions
Provisionally accepted- 1 University of Natural Resources and Life Sciences Vienna, Vienna, Vienna, Austria
- 2 Medical University of Vienna, Vienna, Vienna, Austria
- 3 Other, Hamburg, Germany
- 4 University of Lübeck, Lübeck, Schleswig-Holstein, Germany
- 5 Medical University of Graz, Graz, Styria, Austria
- 6 Leibniz University Hannover, Hanover, Germany
Due to their unique properties, human mesenchymal stem/stromal cells (MSCs) possess tremendous potential in regenerative medicine, particularly in cell-based therapies where the multipotency and immunomodulatory characteristics of MSCs can be leveraged to address a variety of disease states. Although MSC-based cell therapeutics have emerged as one of the most promising medical treatments, the clinical translation is hampered by the variability of MSC-based cellular products caused by tissue source-specific differences and the lack of physiological cell culture approaches that closely mimic the human cellular microenvironment. In this study, a model for trilineage differentiation of primary adipose-, bone marrow- and umbilical cord-derived MSCs into adipocytes, chondrocytes and osteoblasts was established and characterized. Differentiation was performed in spheroids culture, using hypoxic conditions and serum-free and antibiotics-free medium. This platform was characterized for spheroid diameter and trilineage differentiation capacity reflecting functionality of differentiated cells, as indicated by lineage-specific extracellular matrix (ECM) accumulation and expression of distinct secreted markers. The presented model shows spheroid growth during the course of differentiation and successfully supports trilineage differentiation for MSCs from almost all tissue sources except for osteogenesis of umbilical cord-derived MSCs. These findings indicate that this platform provides a suitable and favorable environment for trilineage differentiation of MSCs from various tissue sources. Therefore, it poses a promising model to generate highly relevant biological data urgently required for clinical translation and therefore might be used in the future to generate in vitro microtissues, building blocks for tissue engineering or as disease models.
Keywords: Mesenchymal Stem Cells, Trilineage differentiation, spheroid, hypoxia, Serum-free culture
Received: 05 Jun 2024; Accepted: 12 Jul 2024.
Copyright: © 2024 Moldaschl, Chariyev-Prinz, Toegel, Keck, Hiden, Egger and Kasper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dominik Egger, Leibniz University Hannover, Hanover, Germany
Cornelia Kasper, University of Natural Resources and Life Sciences Vienna, Vienna, 1180, Vienna, Austria
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Maike Keck
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