University of Oulu

Uzieliene, I., Bagdonas, E., Hoshi, K. et al. Different phenotypes and chondrogenic responses of human menstrual blood and bone marrow mesenchymal stem cells to activin A and TGF-β3. Stem Cell Res Ther 12, 251 (2021).

Different phenotypes and chondrogenic responses of human menstrual blood and bone marrow mesenchymal stem cells to activin A and TGF-β3

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Author: Uzieliene, Ilona1; Bagdonas, Edvardas1; Hoshi, Kazuto2,3;
Organizations: 1Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, LT-08406, Vilnius, Lithuania
2Department of Sensory and Motor System Medicine, Department of Oral-maxillofacial Surgery, Dentistry and Orthodontics, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
3Department of Tissue Engineering, the University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-8655, Japan
4Faculty of Medicine, Vilnius University, Vilnius, Lithuania
5Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FI-90014, Oulu, Finland
6Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 508 GA, Utrecht, The Netherlands
7Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-07-07


Background: Due to its low capacity for self-repair, articular cartilage is highly susceptible to damage and deterioration, which leads to the development of degenerative joint diseases such as osteoarthritis (OA). Menstrual blood-derived mesenchymal stem/stromal cells (MenSCs) are much less characterized, as compared to bone marrow mesenchymal stem/stromal cells (BMMSCs). However, MenSCs seem an attractive alternative to classical BMMSCs due to ease of access and broader differentiation capacity. The aim of this study was to evaluate chondrogenic differentiation potential of MenSCs and BMMSCs stimulated with transforming growth factor β (TGF-β3) and activin A.

Methods: MenSCs (n = 6) and BMMSCs (n = 5) were isolated from different healthy donors. Expression of cell surface markers CD90, CD73, CD105, CD44, CD45, CD14, CD36, CD55, CD54, CD63, CD106, CD34, CD10, and Notch1 was analyzed by flow cytometry. Cell proliferation capacity was determined using CCK-8 proliferation kit and cell migration ability was evaluated by scratch assay. Adipogenic differentiation capacity was evaluated according to Oil-Red staining and osteogenic differentiation according to Alizarin Red staining. Chondrogenic differentiation (activin A and TGF-β3 stimulation) was investigated in vitro and in vivo (subcutaneous scaffolds in nude BALB/c mice) by expression of chondrogenic genes (collagen type II, aggrecan), GAG assay and histologically. Activin A protein production was evaluated by ELISA during chondrogenic differentiation in monolayer culture.

Results: MenSCs exhibited a higher proliferation rate, as compared to BMMSCs, and a different expression profile of several cell surface markers. Activin A stimulated collagen type II gene expression and glycosaminoglycan synthesis in TGF-β3 treated MenSCs but not in BMMSCs, both in vitro and in vivo, although the effects of TGF-β3 alone were more pronounced in BMMSCs in vitro.

Conclusion: These data suggest that activin A exerts differential effects on the induction of chondrogenic differentiation in MenSCs vs. BMMSCs, which implies that different mechanisms of chondrogenic regulation are activated in these cells. Following further optimization of differentiation protocols and the choice of growth factors, potentially including activin A, MenSCs may turn out to be a promising population of stem cells for the development of cell-based therapies with the capacity to stimulate cartilage repair and regeneration in OA and related osteoarticular disorders.

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Series: Stem cell research & therapy
ISSN: 1757-6512
ISSN-E: 1757-6512
ISSN-L: 1757-6512
Volume: 12
Issue: 1
Article number: 251
DOI: 10.1186/s13287-021-02286-w
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
318 Medical biotechnology
Funding: This work was funded by Lithuanian Research Council (LMTLT) “Development of injectable biomimetic hydrogels for engineering of cartilage tissue,” P-LLT-18-21, agreement No S-LLT-18-4. Scientific trip to Tokyo university hospital was funded by European structural funds Nr. 09.3.3.-LMT-K-712-14-0144.
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