Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles

Targeted cell delivery by a magnetically actuated microrobot with a porous structure is a promising technique to enhance the low targeting efficiency of mesenchymal stem cell (MSC) in tissue regeneration. However, the relevant research performed to date is only in its proof-of-concept stage. To use the microrobot in a clinical stage, biocompatibility and biodegradation materials should be considered in the microrobot, and its efficacy needs to be verified using an in vivo model. In this study, we propose a human adipose–derived MSC–based medical microrobot system for knee cartilage regeneration and present an in vivo trial to verify the efficacy of the microrobot using the cartilage defect model. The microrobot system consists of a microrobot body capable of supporting MSCs, an electromagnetic actuation system for three-dimensional targeting of the microrobot, and a magnet for fixation of the microrobot to the damaged cartilage. Each component was designed and fabricated considering the accessibility of the patient and medical staff, as well as clinical safety. The efficacy of the microrobot system was then assessed in the cartilage defect model of rabbit knee with the aim to obtain clinical trial approval.

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Promoting Effect of Basic Fibroblast Growth Factor in Synovial Mesenchymal Stem Cell-Based Cartilage Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22010300 ◽

2020 ◽

Vol 22 (1) ◽

pp. 300

Author(s):

Gensuke Okamura ◽

Kosuke Ebina ◽

Makoto Hirao ◽

Ryota Chijimatsu ◽

Yasukazu Yonetani ◽

...

Keyword(s):

Stem Cell ◽

Growth Factor ◽

Mesenchymal Stem Cell ◽

Fibroblast Growth Factor ◽

Basic Fibroblast Growth Factor ◽

Cartilage Regeneration ◽

Fibroblast Growth ◽

Promoting Effect ◽

And Cartilage

Synovial mesenchymal stem cell (SMSC) is the promising cell source of cartilage regeneration but has several issues to overcome such as limited cell proliferation and heterogeneity of cartilage regeneration ability. Previous reports demonstrated that basic fibroblast growth factor (bFGF) can promote proliferation and cartilage differentiation potential of MSCs in vitro, although no reports show its beneficial effect in vivo. The purpose of this study is to investigate the promoting effect of bFGF on cartilage regeneration using human SMSC in vivo. SMSCs were cultured with or without bFGF in a growth medium, and 2 × 105 cells were aggregated to form a synovial pellet. Synovial pellets were implanted into osteochondral defects induced in the femoral trochlea of severe combined immunodeficient mice, and histological evaluation was performed after eight weeks. The presence of implanted SMSCs was confirmed by the observation of human vimentin immunostaining-positive cells. Interestingly, broad lacunae structures and cartilage substrate stained by Safranin-O were observed only in the bFGF (+) group. The bFGF (+) group had significantly higher O’Driscoll scores in the cartilage repair than the bFGF (−) group. The addition of bFGF to SMSC growth culture may be a useful treatment option to promote cartilage regeneration in vivo.

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Faculty of 1000 evaluation for Functional mesenchymal stem cell niches in the adult knee joint synovium in vivo.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.8164968.8640057 ◽

2011 ◽

Author(s):

Frank Barry ◽

Mary Murphy

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Knee Joint ◽

Stem Cell Niches

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Exploiting Stem Cell-Extracellular Matrix Interactions for Cartilage Regeneration: A Focus on Basement Membrane Molecules

Current Stem Cell Research & Therapy ◽

10.2174/1574888x10666150723150525 ◽

2016 ◽

Vol 11 (8) ◽

pp. 618-625 ◽

Cited By ~ 4

Author(s):

Wei Seong Toh ◽

Casper Bindzus Foldager ◽

James Hoi Po Hui ◽

Bjorn Reino Olsen ◽

Myron Spector

Keyword(s):

Extracellular Matrix ◽

Stem Cell ◽

Basement Membrane ◽

Cartilage Regeneration ◽

Matrix Interactions ◽

Extracellular Matrix Interactions

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Cell-free decellularized cartilage extracellular matrix scaffolds combined with interleukin 4 promote osteochondral repair through immunomodulatory macrophages: in vitro and in vivo preclinical study

Acta Biomaterialia ◽

10.1016/j.actbio.2021.03.054 ◽

2021 ◽

Author(s):

Guangzhao Tian ◽

Shuangpeng Jiang ◽

Junqi Li ◽

Fu Wei ◽

Xu Li ◽

...

Keyword(s):

Extracellular Matrix ◽

Preclinical Study ◽

Interleukin 4 ◽

Osteochondral Repair ◽

Cartilage Extracellular Matrix ◽

Extracellular Matrix Scaffolds

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Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02064-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Dongli Li ◽

Junxiu Zhang ◽

Zijia Liu ◽

Yuanyuan Gong ◽

Zhi Zheng

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Umbilical Cord ◽

Mechanism Of Action ◽

Epithelial Mesenchymal Transition ◽

Human Umbilical Cord ◽

Mesenchymal Transition ◽

Rpe Cells ◽

Subretinal Fibrosis

Abstract Background and aim Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo. Methods In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays. Results This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression. Conclusions The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.

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