Effect of intra-articular injection of adipose stem cells on traumatic osteoarthritis cartilage defects

2021 ◽  
Vol 11 (1) ◽  
pp. 28-37
Author(s):  
Qian Wang ◽  
Na Yang ◽  
Kun Zhang ◽  
Zhong Li ◽  
Yangjun Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cartilage Repair ◽  
Cartilage Defect ◽  
Osteoblastic Differentiation ◽  
Left Knee ◽  
Inflammatory Factors ◽  
Cartilage Defects ◽  
Osteoarthritis Cartilage

Traumatic osteoarthritis with cartilage defects can lead to mobility problems. Mitotic activity in cartilage is extremely low, and once damaged, repairing can be difficult. The commonly used autologous or allogeneic cartilage transplantation techniques also have certain limitations. In recent years, directed induction of osteoblastic differentiation using adipocytes has been shown to be effective in repairing cartilage defects. However, it is often induced in vitro and is prone to incomplete or over-differentiation. In addition, because of the large differences in the in vivo and in vitro microenvironment, exploring the influence of these differences in the in vivo microenvironment on the directional differentiation of adipose-derived stem cells (ADSCs) and their effect on cartilage repair is necessary. In this study, a cartilage defect model in rabbits with traumatic osteoarthritis of the left knee was established, and different interventions were conducted in different groups. We determined the effect of directly injecting ADSCs into the joints on repairing cartilage defects in rabbits with traumatic osteoarthritis and analyzed the differences in repair time of newly developed cartilage defects and old cartilage frontal defects. The results indicated that the placement of a stent and injection of ADSCs improved the knee joint activity, increased the expression of BMP and TGF-β protein, and reduced the expression of inflammatory factors, including IL-1β, IL-6, IL-17, and TNF-α. No difference was found between the new cartilage defect and the old one. By directly observing the cartilage defect, intervention with ADSCs + scaffold increased the connection between the cartilage defect and the normal tissue and improved the cartilage repair effect. These results indicated that directly injecting ADSCs into the joints is an effective approach for repairing cartilage defects in traumatic osteoarthritis, and it was not affected by the age of the defect.

Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect

2013 ◽  
Vol 815 ◽  
pp. 345-349 ◽  
Author(s):  
Ching Wen Hsu ◽  
Ping Liu ◽  
Song Song Zhu ◽  
Feng Deng ◽  
Bi Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Defect ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
Cartilage Defects

Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

scholarly journals Intra-articular Injection of SHP2 Inhibitor SHP099 Promotes the Repair of Rabbit Full-thickness Cartilage Defect

2021 ◽  
Author(s):  
Ziying Sun ◽  
Xingquan Xu ◽  
Zhongyang Lv ◽  
Jiawei Li ◽  
Heng Sun ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cartilage Repair ◽  
Normal Saline ◽  
Cartilage Defect ◽  
Cartilage Defects ◽  
Therapeutic Drug ◽  
Full Thickness ◽  
Differentiation Potential

Abstract Background Cartilage repair has been a challenge in the field of orthopedics for decades, highlighting the great significance of investigating potential therapeutic drugs. In this study, we explored the effect of SHP2 inhibitor, SHP099, as a small molecule drug on cartilage repair.Methods Human synovial mesenchymal stem cells (SMSCs) were isolated and their three-way differentiation potential was examined. After treated with chondrogenic medium, the chondrogenic effect of SHP099 on SMSCs was examined by Western blot, qPCR, and immunofluorescence (IF). To explore chondrogenic effects of SHP099 in vivo, full-thickness cartilage defects with microfracture were constructed in the right femoral trochlear of New Zealand White rabbits. Intra-articular injection of SHP099 or normal saline were performed twice a week for 6 weeks. Cartilage repair were evaluated by hematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining. Immunohistochemistry (IHC) for collagen II (COL2) was also conducted to verify the abandance of cartilage extracellular matrix after SHP099 treatment. The mechanism involving yes associated protein (YAP) and WNT signaling was investigated in vitro.Result The SMSCs isolated from human synovium represented optimal multi-differentiation potential. SHP099 increased chondrogenic markers (SOX9, COL2) expression and decreased hypertrophic markers (COL10, RUNX2) in SMSCs. The inhibition of YAP and WNT signaling was also observed. Moreover, compared with the normal saline group at 6 weeks, intra-articular injection of SHP099 resulted in better defect filling which formed more hyaline cartilage-like tissue with more glycosaminoglycan (GAG) and COL2.Conclusion SHP099 promotes the repair of rabbit full-thickness cartilage defect, representing a potential therapeutic drug for cartilage repair.

scholarly journals Comparison of chondrogenesis-related biological behaviors between human urine-derived stem cells and human bone marrow mesenchymal stem cells from the same individual

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiachen Sun ◽  
Fei Xing ◽  
Min Zou ◽  
Min Gong ◽  
Lang Li ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cartilage Repair ◽  
Cartilage Defects ◽  
In Vitro Experiments ◽  
Rabbit Knee ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Stem cells are the main choice for seed cells in tissue engineering, but using most traditional stem cells requires invasive and complicated procedures. Human urine-derived stem cells (hUSCs) are an alternative stem cell source with the advantages of being isolated noninvasively and repetitively from the same individual. The aim of this study was to compare chondrogenesis-related biological behaviors between hUSCs and human bone marrow mesenchymal stem cells (hBMSCs) from the same individual. Methods hUSCs and hBMSCs were isolated from six patients who underwent iliac bone grafting. Cell morphology, proliferation, colony-forming, migration, and multidifferentiation analyses were performed in vitro. Then, acellular cartilage extracellular matrix (ACM) scaffolds were fabricated for in vivo implantation. The comparisons of cell viability, morphology, proliferation, and chondrogenesis between hUSCs and hBMSCs cultured on scaffolds were performed before implantation. The scaffolds loaded with hUSCs or hBMSCs were implanted into a rabbit knee model to repair cartilage defects. Magnetic resonance imaging (MRI) and micro-computed tomography (μCT) Analyses, inflammation and toxicity assays, gross observation, and histological evaluation were performed to evaluate the cartilage repair effects. Results In in vitro experiments, hUSCs had better capacity for proliferation, colony-forming, and migration compared to hBMSCs in the same passage, while hBMSCs had greater osteogenic, adipogenic, and chondrogenic abilities compared to hUSCs in the same passage. Both hUSCs and hBMSCs at passage 3 had the strongest potential for proliferation, colony-forming, and multilineage differentiation compared to cells in other passages. The ACM scaffolds loaded with hUSCs or hBMSCs both significantly promoted the repair of cartilage defects in the rabbit knee model at 12 weeks’ postimplantation, and the new tissue was mainly hyaline cartilage. However, there was no significant difference in cartilage repair effects between hUSCs and hBMSCs. Conclusions In in vitro experiments, hUSCs presented better capacity for proliferation, while hBMSCs had greater chondrogenic ability. However, hUSCs and hBMSCs had similar cartilage repair effects in vivo. Results indicated that hUSCs can be a stem cell alternative for cartilage regeneration and provide a powerful platform for cartilage tissue engineering and clinical transformation. Graphical abstract

scholarly journals A composite scaffold of Wharton’s jelly and chondroitin sulphate loaded with human umbilical cord mesenchymal stem cells repairs articular cartilage defects in rat knee

2021 ◽  
Vol 32 (4) ◽  
Author(s):  
Zhong Li ◽  
Yikang Bi ◽  
Qi Wu ◽  
Chao Chen ◽  
Lu Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Composite Scaffold ◽  
Biomechanical Properties ◽  
Cartilage Defects ◽  
Human Umbilical Cord ◽  
Composite Scaffolds ◽  
Articular Cartilage Defects

AbstractTo evaluate the performance of a composite scaffold of Wharton’s jelly (WJ) and chondroitin sulfate (CS) and the effect of the composite scaffold loaded with human umbilical cord mesenchymal stem cells (hUCMSCs) in repairing articular cartilage defects, two experiments were carried out. The in vitro experiments involved identification of the hUCMSCs, construction of the biomimetic composite scaffolds by the physical and chemical crosslinking of WJ and CS, and testing of the biomechanical properties of both the composite scaffold and the WJ scaffold. In the in vivo experiments, composite scaffolds loaded with hUCMSCs and WJ scaffolds loaded with hUCMSCs were applied to repair articular cartilage defects in the rat knee. Moreover, their repair effects were evaluated by the unaided eye, histological observations, and the immunogenicity of scaffolds and hUCMSCs. We found that in vitro, the Young’s modulus of the composite scaffold (WJ-CS) was higher than that of the WJ scaffold. In vivo, the composite scaffold loaded with hUCMSCs repaired rat cartilage defects better than did the WJ scaffold loaded with hUCMSCs. Both the scaffold and hUCMSCs showed low immunogenicity. These results demonstrate that the in vitro construction of a human-derived WJ-CS composite scaffold enhances the biomechanical properties of WJ and that the repair of knee cartilage defects in rats is better with the composite scaffold than with the single WJ scaffold if the scaffold is loaded with hUCMSCs.

scholarly journals Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Articular Cartilage ◽  
Synovial Fluid ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Large Animal

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.

scholarly journals Repair of an Osteochondral Defect With Minced Cartilage Embedded in Atelocollagen Gel: A Rabbit Model

2019 ◽  
Vol 47 (9) ◽  
pp. 2216-2224 ◽  
Author(s):  
Ryosuke Matsushita ◽  
Tomoyuki Nakasa ◽  
Masakazu Ishikawa ◽  
Yusuke Tsuyuguchi ◽  
Norimasa Matsubara ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Rabbit Model ◽  
Cartilage Defects ◽  
Trochlear Groove ◽  
Periosteal Flap ◽  
Significant Difference ◽  
Chondrocyte Migration

Background: Autologous chondrocyte implantation (ACI) is often performed for large cartilage defects. Because this technique has several disadvantages, including the need for second-stage surgery, cartilage repair using minced cartilage has been suggested. However, this technique could be improved using 3-dimensional scaffolds. Purpose: To examine the ability of chondrocyte migration and proliferation from minced cartilage in atelocollagen gel in vitro and evaluate the repairable potential of minced cartilage embedded in atelocollagen gel covered with a periosteal flap in a rabbit model. Study Design: Controlled laboratory study. Methods: Minced cartilage or isolated chondrocytes from rabbits were embedded in atelocollagen gel and cultured for 3 weeks. Chondrocyte proliferation and matrix production were evaluated in vitro. An osteochondral defect at the trochlear groove was created in 56 rabbits, which were divided into 4 groups. The defect was left empty (defect group), filled with allogenic minced cartilage (minced cartilage group), filled with isolated allogenic chondrocytes embedded in atelocollagen gel (ACI group), or filled with atelocollagen gel (atelocollagen with periosteal flap group). At 4, 12, and 24 weeks after surgery, repair of the defect was evaluated in these 4 groups. Results: In vitro, the number of chondrocytes and abundant matrix on the surface of the gel significantly increased in the minced cartilage group compared with the ACI group ( P < .05). In vivo, the minced cartilage and ACI groups showed good cartilage repair compared with the empty defect and atelocollagen/periosteal flap groups ( P < .05); there was no significant difference in the Pineda score between the minced cartilage and ACI groups. Conclusion: Minced cartilage in atelocollagen gel had good chondrocyte migration and proliferation abilities in vitro, and osteochondral defects were well repaired by implanting minced cartilage embedded in the atelocollagen gel in vivo. Implantation of minced cartilage embedded in atelocollagen gel showed good cartilage repair equivalent to ACI. Clinical Relevance: Implantation of minced cartilage embedded in atelocollagen gel as a 1-step procedure has outcomes similar to those of ACI but is cheaper and more convenient than ACI.

scholarly journals Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 230
Author(s):  
Girish Pattappa ◽  
Jonas Krueckel ◽  
Ruth Schewior ◽  
Dustin Franke ◽  
Alexander Mench ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Repair ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Large Animal ◽  
Large Animal Models ◽  
Early Oa

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

scholarly journals In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianhua Yang ◽  
Xiaoguang Jing ◽  
Zimin Wang ◽  
Xuejian Liu ◽  
Xiaofeng Zhu ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Polyethylene Glycol ◽  
Knee Joint ◽  
Cartilage Defect ◽  
Positive Control ◽  
Cartilage Defects ◽  
Control Group ◽  
Glycol Chitosan

The normal anatomical structure of articular cartilage determines its limited ability to regenerate and repair. Once damaged, it is difficult to repair it by itself. How to realize the regeneration and repair of articular cartilage has always been a big problem for clinicians and researchers. Here, we conducted a comprehensive analysis of the physical properties and cytocompatibility of hydrogels, and evaluated their feasibility as cell carriers for Adipose-derived mesenchymal stem cell (ADSC) transplantation. Concentration-matched hydrogels were co-cultured with ADSCs to confirm ADSC growth in the hydrogel and provide data supporting in vivo experiments, which comprised the hydrogel/ADSCs, pure-hydrogel, defect-placement, and positive-control groups. Rat models of articular cartilage defect in the knee joint region was generated, and each treatment was administered on the knee joint cartilage area for each group; in the positive-control group, the joint cavity was surgically opened, without inducing a cartilage defect. The reparative effect of injectable glycol chitosan/dibenzaldehyde-terminated polyethylene glycol (GCS/DF-PEG) hydrogel on injured articular cartilage was evaluated by measuring gross scores and histological score of knee joint articular-cartilage injury in rats after 8 weeks. The 1.5% GCS/2% DF-PEG hydrogels degraded quickly in vitro. Then, We perform in vivo and in vitro experiments to evaluate the feasibility of this material for cartilage repair in vivo and in vitro.

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