Evaluation of tenogenic differentiation potential of selected subpopulations of human adipose-derived stem cells
Ana I. Gonçalves
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
Search for more papers by this authorDominika Berdecka
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
Search for more papers by this authorMárcia T. Rodrigues
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
Search for more papers by this authorAysegul Dede Eren
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht, The Netherlands
Search for more papers by this authorJan de Boer
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht, The Netherlands
Search for more papers by this authorRui L. Reis
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
Search for more papers by this authorCorresponding Author
Manuela E. Gomes
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
Correspondence
Manuela E. Gomes, 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.
Email: [email protected]
Search for more papers by this authorAna I. Gonçalves
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
Search for more papers by this authorDominika Berdecka
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
Search for more papers by this authorMárcia T. Rodrigues
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
Search for more papers by this authorAysegul Dede Eren
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht, The Netherlands
Search for more papers by this authorJan de Boer
MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht, The Netherlands
Search for more papers by this authorRui L. Reis
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
Search for more papers by this authorCorresponding Author
Manuela E. Gomes
3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
ICVS/3B's–PT Government Associate Laboratory, Braga, Portugal
The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
Correspondence
Manuela E. Gomes, 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal.
Email: [email protected]
Search for more papers by this authorAbstract
Identification of a suitable cell source and bioactive agents guiding cell differentiation towards tenogenic phenotype represents a prerequisite for advancement of cell-based therapies for tendon repair. Human adipose-derived stem cells (hASCs) are a promising, yet intrinsically heterogenous population with diversified differentiation capacities. In this work, we investigated antigenically-defined subsets of hASCs expressing markers related to tendon phenotype or associated with pluripotency that might be more prone to tenogenic differentiation, when compared to unsorted hASCs. Subpopulations positive for tenomodulin (TNMD+ hASCs) and stage specific early antigen 4 (SSEA-4+ hASCs), as well as unsorted ASCs were cultured up to 21 days in basic medium or media supplemented with TGF-β3 (10 ng/ml), or GDF-5 (50 ng/ml). Cell response was evaluated by analysis of expression of tendon-related markers at gene level and protein level by real time RT-PCR, western blot, and immunocytochemistry. A significant upregulation of scleraxis was observed for both subpopulations and unsorted hASCs in the presence of TGF-β3. More prominent alterations in gene expression profile in response to TGF-β3 were observed for TNMD+ hASCs. Subpopulations evidenced an increased collagen III and TNC deposition in basal medium conditions in comparison with unsorted hASCs. In the particular case of TNMD+ hASCs, GDF-5 seems to influence more the deposition of TNC. Within hASCs populations, discrete subsets could be distinguished offering varied sensitivity to specific biochemical stimulation leading to differential expression of tenogenic components suggesting that cell subsets may have distinctive roles in the complex biological responses leading to tenogenic commitment to be further explored in cell based strategies for tendon tissues.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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