Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy
Background: Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported.
Results: We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy.
Conclusions: C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.
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Fig. S1 The DNA and GAG contents were stained for the Hoechst 33258 and dimethyl methylene blue dye binding assays, respectively, after 3, 7, 14, and 21 days of HUCMSCs treatment with negative control, C-EVs, and TGF-β. The absorbances were measured to quantify the contents of DNA (A) and GAG (B). These data are presented as the means ± SD of three independent experiments. *p <0.05, **p <0.01, ***p <0.001.
Posted 23 Sep, 2020
Received 14 Aug, 2020
On 14 Aug, 2020
On 10 Aug, 2020
Invitations sent on 06 Aug, 2020
On 05 Aug, 2020
On 04 Aug, 2020
On 04 Aug, 2020
On 30 Jun, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
On 23 Apr, 2020
Invitations sent on 21 Apr, 2020
On 21 Apr, 2020
On 19 Apr, 2020
On 19 Apr, 2020
On 18 Apr, 2020
On 17 Apr, 2020
Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy
Posted 23 Sep, 2020
Received 14 Aug, 2020
On 14 Aug, 2020
On 10 Aug, 2020
Invitations sent on 06 Aug, 2020
On 05 Aug, 2020
On 04 Aug, 2020
On 04 Aug, 2020
On 30 Jun, 2020
Received 30 Apr, 2020
Received 30 Apr, 2020
On 23 Apr, 2020
Invitations sent on 21 Apr, 2020
On 21 Apr, 2020
On 19 Apr, 2020
On 19 Apr, 2020
On 18 Apr, 2020
On 17 Apr, 2020
Background: Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported.
Results: We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy.
Conclusions: C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7