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Research
Hypoxic ADSCs-derived EVs Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells
ke xue
Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai 200011, PR China
Corresponding Author
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Background： Cartilage tissue engineering is a promising option for repairing cartilage defects caused by trauma, inflammation and osteoarthritis, although harvesting a large number of seeding cells with stable phenotypes remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles secreted by mesenchymal stem cells may play a major role in cell-cell and tissue-tissue communication by transporting various RNAs and proteins in mesenchymal stem cell-based therapy. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived extracellular vesicles (EVs) on CSPCs proliferation and differentiation.
Methods: The characteristics of ADSCs-derived EVs were identified by and flow cytometric analysis. Proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. The effect of ADSC-derived EVs on CSPCs were evaluated in alginate hydrogel culture, and SEM, histological staining, biochemical and biomechanical analysis were performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture.
Results: The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40–1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induced CSPCs to produce significantly more cartilage matrix and proteoglycan.
Conclusions: The present study indicated that hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.
Keywords
Cartilage stem/progenitor cells, extracellular vesicles, hypoxic adipose-derived stem cells, cartilage tissue engineering, proliferation, differentiation
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Research
Hypoxic ADSCs-derived EVs Promote the Proliferation and Chondrogenic Differentiation of Cartilage Stem/progenitor Cells
ke xue
Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai 200011, PR China
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 16 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Stem Cell & Developmental Cell Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background： Cartilage tissue engineering is a promising option for repairing cartilage defects caused by trauma, inflammation and osteoarthritis, although harvesting a large number of seeding cells with stable phenotypes remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles secreted by mesenchymal stem cells may play a major role in cell-cell and tissue-tissue communication by transporting various RNAs and proteins in mesenchymal stem cell-based therapy. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived extracellular vesicles (EVs) on CSPCs proliferation and differentiation.
Methods: The characteristics of ADSCs-derived EVs were identified by and flow cytometric analysis. Proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. The effect of ADSC-derived EVs on CSPCs were evaluated in alginate hydrogel culture, and SEM, histological staining, biochemical and biomechanical analysis were performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture.
Results: The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40–1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induced CSPCs to produce significantly more cartilage matrix and proteoglycan.
Conclusions: The present study indicated that hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
Figure 6
Figure 6
Figure 7
Figure 7
Figure 8
Figure 8
Figure 9
Figure 9
Due to technical limitations, table 1 is only available as a download in the Supplemental Files section.