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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.
Keywords
autophagy, chondrocytes, chondrogenesis, extracellular vesicles, human umbilical cord mesenchymal stem cells
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Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
- Sup.Fig1.tif
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.
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CURRENT STATUS: Published
View the published article at Journal of Nanobiotechnology.
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Posted 23 Sep, 2020
No community comments so far
Editorial decision: Accept
On 23 Sep, 2020
Editor assigned
On 22 Sep, 2020
Submission checks complete
On 21 Sep, 2020
Editor invited
On 21 Sep, 2020
No comments provided
Review #1 received
Received 14 Aug, 2020
Editorial decision: Minor revision
On 14 Aug, 2020
Reviewer #1 agreed
On 10 Aug, 2020
Reviewers invited
Invitations sent on 06 Aug, 2020
Editor assigned
On 05 Aug, 2020
Submission checks complete
On 04 Aug, 2020
Editor invited
On 04 Aug, 2020
No comments provided
Editorial decision: Major revision
On 30 Jun, 2020
Review #1 received
Received 30 Apr, 2020
Review #2 received
Received 30 Apr, 2020
Reviewer #2 agreed
On 23 Apr, 2020
Reviewers invited
Invitations sent on 21 Apr, 2020
Reviewer #1 agreed
On 21 Apr, 2020
Editor invited
On 19 Apr, 2020
Editor assigned
On 19 Apr, 2020
Submission checks complete
On 18 Apr, 2020
First submitted
On 17 Apr, 2020
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See the published version of this preprint at Journal of Nanobiotechnology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Nanobiotechnology.
Version 3
Posted 23 Sep, 2020
No community comments so far
Editorial decision: Accept
On 23 Sep, 2020
Editor assigned
On 22 Sep, 2020
Submission checks complete
On 21 Sep, 2020
Editor invited
On 21 Sep, 2020
No comments provided
Review #1 received
Received 14 Aug, 2020
Editorial decision: Minor revision
On 14 Aug, 2020
Reviewer #1 agreed
On 10 Aug, 2020
Reviewers invited
Invitations sent on 06 Aug, 2020
Editor assigned
On 05 Aug, 2020
Submission checks complete
On 04 Aug, 2020
Editor invited
On 04 Aug, 2020
No comments provided
Editorial decision: Major revision
On 30 Jun, 2020
Review #1 received
Received 30 Apr, 2020
Review #2 received
Received 30 Apr, 2020
Reviewer #2 agreed
On 23 Apr, 2020
Reviewers invited
Invitations sent on 21 Apr, 2020
Reviewer #1 agreed
On 21 Apr, 2020
Editor invited
On 19 Apr, 2020
Editor assigned
On 19 Apr, 2020
Submission checks complete
On 18 Apr, 2020
First submitted
On 17 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Nanobiotechnology.
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
This is a list of supplementary files associated with this preprint. Click to download.
- Sup.Fig1.tif
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.
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