scholarly journals Characterization of chondrocyte scaffold carriers for cell-based gene therapy in articular cartilage repair

2013 ◽  
Vol 101 (12) ◽  
pp. 3542-3550 ◽  
Author(s):  
Wei Shui ◽  
Liangjun Yin ◽  
Jeffrey Luo ◽  
Ruidong Li ◽  
Wenwen Zhang ◽  
...  
2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Miki Maehara ◽  
Masato Sato ◽  
Eriko Toyoda ◽  
Takumi Takahashi ◽  
Eri Okada ◽  
...  

2003 ◽  
Vol 48 (2) ◽  
pp. 430-441 ◽  
Author(s):  
Kolja Gelse ◽  
Klaus von der Mark ◽  
Thomas Aigner ◽  
Jung Park ◽  
Holm Schneider

Author(s):  
Alan Ivkovic ◽  
Andreja Vukasovic ◽  
Ryan M. Porter ◽  
Damir Hudetz ◽  
Marko Pecina ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junjun Shi ◽  
Xin Zhang ◽  
Yanbin Pi ◽  
Jingxian Zhu ◽  
Chunyan Zhou ◽  
...  

The clinical application of viral vectors for gene therapy is limited for biosafety consideration. In this study, to promote articular cartilage repair, poly (lactic-co glycolic acid) (PLGA) nanopolymers were used as non-viral vectors to transfect rabbit mesenchymal stem cells (MSCs) with the pDC316-BMP4-EGFP plasmid. The cytotoxicity and transfection efficiency in vitro were acceptable measuring by CCK-8 and flow cytometry. After transfection, Chondrogenic markers (mRNA of Col2a1, Sox9, Bmp4, and Agg) of experimental cells (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers) were increased more than those of control cells (MSCs being transfected with naked BMP-4 plasmid alone). In vivo study, twelve rabbits (24 knees) with large full thickness articular cartilage defects were randomly divided into the experimental group (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers) and the control group (MSCs being transfected with naked BMP-4 plasmid). The experimental group showed better regeneration than the control group 6 and 12 weeks postoperatively. Hyaline-like cartilage formed at week 12 in the experimental group, indicating the local delivery of BMP-4 plasmid to MSCs by PLGA nanopolymers improved articular cartilage repair significantly. PLGA nanopolymers could be a promising and effective non-viral vector for gene therapy in cartilage repair.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xueqin Gao ◽  
Haizi Cheng ◽  
Hassan Awada ◽  
Ying Tang ◽  
Sarah Amra ◽  
...  

Abstract Background Osteoarthritis and cartilage injury treatment is an unmet clinical need. Therefore, development of new approaches to treat these diseases is critically needed. Previous work in our laboratory has shown that murine muscle-derived stem cells (MDSCs) can efficiently repair articular cartilage in an osteochondral and osteoarthritis model. However, the cartilage repair capacity of human muscle-derived stem cells has not been studied which prompt this study. Method In this study, we tested the in vitro chondrogenesis ability of six populations of human muscle-derived stem cells (hMDSCs), before and after lenti-BMP2/GFP transduction using pellet culture and evaluated chondrogenic differentiation of via histology and Raman spectroscopy. We further compared the in vivo articular cartilage repair of hMDSCs stimulated with BMP2 delivered through coacervate sustain release technology and lenti-viral gene therapy-mediated gene delivery in a monoiodoacetate (MIA)-induced osteoarthritis (OA) model. We used microCT and histology to evaluate the cartilage repair. Results We observed that all hMDSCs were able to undergo chondrogenic differentiation in vitro. As expected, lenti-BMP2/GFP transduction further enhanced the chondrogenic differentiation capacities of hMDSCs, as confirmed by Alcian blue and Col2A1staining as well as Raman spectroscopy analysis. We observed through micro-CT scanning, Col2A1 staining, and histological analyses that delivery of BMP2 with coacervate could achieve a similar articular cartilage repair to that mediated by hMDSC-LBMP2/GFP. We also found that the addition of soluble fms-like tyrosine kinase-1 (sFLT-1) protein further improved the regenerative potential of hMDSCs/BMP2 delivered through the coacervate sustain release technology. Donor cells did not primarily contribute to the repaired articular cartilage since most of the repair cells are host derived as indicated by GFP staining. Conclusions We conclude that the delivery of hMDSCs and BMP2 with the coacervate technology can achieve a similar cartilage repair relative to lenti-BMP2/GFP-mediated gene therapy. The use of coacervate technology to deliver BMP2/sFLT1 with hMDSCs for cartilage repair holds promise for possible clinical translation into an effective treatment modality for osteoarthritis and traumatic cartilage injury.


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