Overexpressing Runx2 of BMSCs Improves the Repairment of knee Cartilage Defects

2020 ◽  
Vol 20 (5) ◽  
pp. 395-404
Author(s):  
Jing Hu ◽  
Wen-Zhong Zou ◽  
Ling Li ◽  
Zheng-shuai Shi ◽  
Xiang-Zhong Liu ◽  
...  

Background: Recruitment of gene modifying bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single-cell injection in articular cartilage repair. Purpose: This study aimed to investigate whether the effect of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. Methods: Thirty-two New Zealand rabbits were randomly divided into four groups. The blank group (Con) did not receive anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, and the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of the medial femoral condyle. Cell and saline injections were performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. Results: Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4th week. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8 weeks in masson trichrome staining. The COL-II, SOX9, and Aggrecan mRNA expressions of MSCs were enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-IIand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than the Mo level (P<0.05). The IL-1β content in the joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). Conclusions: The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, and Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Mohamed E. Awad ◽  
Khaled A. Hussein ◽  
Inas Helwa ◽  
Mohamed F. Abdelsamid ◽  
Alexandra Aguilar-Perez ◽  
...  

The aim of this study is to review all the published clinical trials on autologous bone marrow mesenchymal stem cells (BM-MSCs) in the repair of cartilage lesions of the knee. We performed a comprehensive search in three electronic databases: PubMed, Medline via Ovid, and Web of Science. A systematic review was conducted according to the guidelines of PRISMA protocol and the Cochrane Handbook for Systematic Reviews of Interventions. The modified Coleman methodology score was used to assess the quality of the included studies. Meta-analysis was conducted to estimate the effect size for Pain and function change after receiving BM-MSCs. Thirty-three studies—including 724 patients of mean age 44.2 years—were eligible. 50.7% of the included patients received cultured BM-MSCs for knee cartilage repair. There was improvement in the MINORS quality score over time with a positive correlation with the publication year. Meta-analysis indicated better improvement and statistical significance in the Visual Analog Scale for Pain, IKDC Function, Tegner Activity Scale, and Lysholm Knee Score after administration of noncultured BM-MSCs when compared to evaluation before the treatment. Meanwhile, there was a clear methodological defect in most studies with an average modified Coleman methodology score (MCMS) of 55. BM-MSCs revealed a clinically relevant improvement in pain, function, and histological regeneration.


2019 ◽  
Vol 3 (1) ◽  

The present study was performed to examine the effect of intra- articular injection of bone marrow mesenchymal stem cells (BMMSCs) and chondrogenic differentiated mesenchymal stem cells (CD- MSCs) on the repair of articular cartilage defects in rabbits. Twenty-five adult female baladi rabbits were used in this work. 5 rabbits were used for preparation of bone marrow mesenchymal stem cells (BM-MSCs) and their left knees were not subjected for the surgical procedure and used as normal control group. The remaining twenty rabbits were subjected for surgically induced cartilage defects in their left knees through a small medial parapatellar incision using bone curette. In the next day, the rabbits were divided into four groups: group I was not injected intraarticularly, group II injected intra-articularly by a single dose of saline, group III injected intra-articularly by a single dose of BM-MSCs and group IV injected intra-articularly by a single dose of CD-MSCs. After 8 weeks from the time of intra-articular injection. On time the rabbits were sacrificed and the entire knee joints were excised and examined. Groups I and II showed marked degenerative changes in their articular cartilage. The articular surface healed by fibrocartilage in group III, while in group IV the articular surface healed by hyaline cartilage. Treatment by CD-MSCs promotes a better healing effect on the articular cartilage defects of injured knee joints in rabbit’s model and has a remarkable superiority of repair than BM-MSCs. This can prevent the progress of cartilage defect into osteoarthritis which was a harmful disease.


Author(s):  
Nan Ding ◽  
Ermao Li ◽  
Xiangbin Ouyang ◽  
Jin Guo ◽  
Bo Wei

: Osteoarthritis (OA), characterized by the degeneration and destruction of articular cartilage, is one of the most significant public health issues around the world. In the course of OA, inflammatory response is an important factor leading to cartilage destruction and exacerbation of symptoms. The low immunogenicity, multi-directional differentiation and high portability properties make bone marrow mesenchymal stem cells (BMSCs) ideal seed cells for OA. Here, we review recent literature relating to the application of BMSCs for OA cell therapy and consider the following aspects: migration and homing of BMSCs, immunomodulatory and anti-inflammatory effects of BMSCs, anti-fibrotic effects of BMSCs, the application of biological scaffolds in cartilage regeneration by BMSCs and chondrogenic differentiation of BMSCs. Injecting BMSCs into joints with an inflammatory environment may increase the risk of osteoproliferation and ectopic calcification in patients. Further evidence and studies are needed to ensure the improvement and maintenance of the intraarticular environment for cartilage repair and regeneration.


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