Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

Abstract 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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Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

10.21203/rs.3.rs-23463/v3 ◽

2020 ◽

Author(s):

Ke Ma ◽

Bo Zhu ◽

Zetao Wang ◽

Peian Cai ◽

Mingwei He ◽

...

Keyword(s):

Stem Cells ◽

Umbilical Cord ◽

Extracellular Vesicles ◽

Chondrogenic Differentiation ◽

Phenotypic Expression ◽

Rabbit Model ◽

Cartilage Regeneration ◽

Human Umbilical Cord ◽

Articular Chondrocyte

Abstract 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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Articular chondrocyte-derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

10.21203/rs.3.rs-23463/v2 ◽

2020 ◽

Author(s):

Ke Ma ◽

Bo Zhu ◽

Zetao Wang ◽

Peian Cai ◽

Mingwei He ◽

...

Keyword(s):

Stem Cells ◽

Umbilical Cord ◽

Cartilage Repair ◽

Chondrogenic Differentiation ◽

Phenotypic Expression ◽

Cartilage Regeneration ◽

Human Umbilical Cord ◽

Articular Chondrocyte ◽

Differentiation And Proliferation

Abstract 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 HUMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that exosomes could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived exosomes (C-EXOs) in chondrogenic differentiation of HUCMSCs has not been reported. Results In this study, we successfully isolated chondrocyte-derived exosomes (C-EXO) from human multi-finger cartilage and found that C-EXO efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A and SOX-9. Also, the expression of the fibrotic marker, COL1A and hypertrophic marker, COL10, was significantly lower than that induced by TGF-β. In vivo, stimulation of C-EXO accelerated HUCMSCs-mediated cartilage repair in rabbit models. Furthermore, C-EXO led to increasing autophagosomes during the process of chondrogenic differentiation, indicating that C-EXO promoted cartilage regeneration might be through the activation of autophagy. Conclusions C-EXOs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

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Articular chondrocyte derived exosomes promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

10.21203/rs.3.rs-23463/v1 ◽

2020 ◽

Author(s):

Ke Ma ◽

Bo Zhu ◽

Zetao Wang ◽

Peian Cai ◽

Mingwei He ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Cartilage Repair ◽

Chondrogenic Differentiation ◽

Phenotypic Expression ◽

Cartilage Regeneration ◽

Human Umbilical Cord ◽

Articular Chondrocyte

Abstract Background Umbilical cord mesenchymal stem cells (HUCMSCs)-based therapies were previously predicated in cartilage regeneration due to the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUMSCs is limited by administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported the exosomes could modulate phenotypic expression of stem cells. However, the role of human chondrogenic derived exosomes (C-EXO) in chondrogenic differentiation of HUCMSCs has not been reported. Results In this study, we successfully isolated chondrocyte-derived exosomes (C-EXO) from human multi-finger cartilage and found that C-EXO efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A and SOX-9. Also, the expression of the fibrotic marker, COL1A and hypertrophic marker, COL10, was significantly lower than that induced by TGF-β. In vivo, stimulation of C-EXO accelerated HUCMSCs-mediated cartilage repair in rabbit models. Furthermore, C-EXO led to increasing autophagosomes during the process of chondrogenic differentiation, indicating that C-EXO promoted cartilage regeneration might be through the activation of autophagy. Conclusions This study suggests that C-EXO has an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be a stable supply for articular cartilage repair.

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Microvesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Stimulated by Hypoxia Promote Angiogenesis Both In Vitro and In Vivo

Stem Cells and Development ◽

10.1089/scd.2012.0095 ◽

2012 ◽

Vol 21 (18) ◽

pp. 3289-3297 ◽

Cited By ~ 151

Author(s):

Hong-Chao Zhang ◽

Xin-Bin Liu ◽

Shu Huang ◽

Xiao-Yun Bi ◽

Heng-Xiang Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Human Umbilical Cord

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Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2019.2845 ◽

2019 ◽

Vol 15 (11) ◽

pp. 2179-2192

Author(s):

Yuanyuan Xie ◽

Wei Liu ◽

Bing Zhang ◽

Bin Wang ◽

Liudi Wang ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Umbilical Cord ◽

Cell Tracking ◽

Superparamagnetic Iron Oxide ◽

Human Umbilical Cord ◽

Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

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