scholarly journals Nanopolymers Delivery of the Bone Morphogenetic Protein-4 Plasmid to Mesenchymal Stem Cells Promotes Articular Cartilage Repair In Vitro and In Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Junjun Shi ◽  
Xin Zhang ◽  
Yanbin Pi ◽  
Jingxian Zhu ◽  
Chunyan Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Viral Vectors ◽  
Control Group ◽  
Articular Cartilage Repair ◽  
Experimental Group

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.

scholarly journals A comparison of BMP2 delivery by coacervate and gene therapy for promoting human muscle-derived stem cell-mediated articular cartilage repair

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Xueqin Gao ◽  
Haizi Cheng ◽  
Hassan Awada ◽  
Ying Tang ◽  
Sarah Amra ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Raman Spectroscopy ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Chondrogenic Differentiation ◽  
Human Muscle ◽  
Articular Cartilage Repair ◽  
Sustain Release

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.

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 Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair

Cartilage ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Mariana Lazarini ◽  
Pedro Bordeaux-Rego ◽  
Renata Giardini-Rosa ◽  
Adriana S. S. Duarte ◽  
Mariana Ozello Baratti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Fibrin Sealant ◽  
Type Ii Collagen ◽  
Adipose Derived Stem Cells ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Collagen Hydrogel

Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

scholarly journals Curcumin Supplementation Enhances Bone Marrow Mesenchymal Stem Cells to Promote the Anabolism of Articular Chondrocytes and Cartilage Repair

2021 ◽  
Vol 30 ◽  
pp. 096368972199377
Author(s):  
Rui Zhang ◽  
Qiaoxia Zhang ◽  
Zhiyu Zou ◽  
Zheng Li ◽  
Meng Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Immunofluorescent Staining ◽  
And Migration ◽  
Proliferation And Migration

Mesenchymal stem cells derived from bone marrows (BMSCs) and curcumin derived from turmeric were used for osteoarthritis (OA) treatment, respectively. We invested the effects of curcumin supplementation for BMSC therapeutic effects. In vitro, rat BMSCs were identified by dual-immunofluorescent staining of CD44 and CD90, and flow cytometry. Primary articular chondrocytes were identified by toluidine blue staining and immunofluorescent staining of Col2a1. EdU incorporation, migration assay, real-time quantitative polymerase chain reaction, and Western blot analyses were performed to evaluate the alterations of chondrocytes cocultured with BMSCs. In vivo, the rat model of OA was established by monoiodoacetic acid. After intra-articular injection of allogeneic BMSCs, articular cartilage damage and OA progression were evaluated by histological staining, and Osteoarthritis Research Society International and Mankin score evaluation. Although curcumin alone did not improve cell viability of primary articular chondrocytes, it promoted proliferation and migration of chondrocytes when cocultured with BMSCs. Meanwhile, the expression of anabolic genes in chondrocytes was remarkably increased both at mRNA and protein levels. In OA rats, curcumin and BMSCs cooperated to greatly promote articular cartilage repair and retard OA progression. Therefore, curcumin supplementation enhanced the BMSC function for the proliferation and migration of articular chondrocytes, and anabolic gene expression of extracellular matrix in articular chondrocytes in vitro, and the generation of articular cartilage in vivo. Our study shed light on the potential clinical application of curcumin cooperated with BMSCs in cartilage repair for OA treatment.

Aptamer-Functionalized Bioscaffold Enhances Cartilage Repair by Improving Stem Cell Recruitment in Osteochondral Defects of Rabbit Knees

2019 ◽  
Vol 47 (10) ◽  
pp. 2316-2326 ◽  
Author(s):  
Xin Wang ◽  
Xiongbo Song ◽  
Tao Li ◽  
Jiajia Chen ◽  
Guotao Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Silk Fibroin ◽  
Cartilage Repair ◽  
Osteochondral Defect ◽  
Cartilage Tissue ◽  
Control Group ◽  
Osteochondral Defects ◽  
Scaffold Group

Background: Recruitment of endogenous stem cells has been considered an alternative to cell injection/implantation in articular cartilage repair. Purpose: (1) To develop a cartilage tissue-engineering scaffold with clinically available biomaterials and functionalize the scaffold with an aptamer (Apt19s) that specifically recognizes pluripotent stem cells. (2) To determine whether this scaffold could recruit joint-resident mesenchymal stem cells (MSCs) when implanted into an osteochondral defect in a rabbit model and to examine the effects of cartilage regeneration. Study Design: Controlled laboratory study. Methods: The reinforced scaffold was fabricated by embedding a silk fibroin sponge into silk fibroin/hyaluronic acid–tyramine hydrogel and characterized in vitro. A cylindrical osteochondral defect (3.2 mm wide × 4 mm deep) was created in the trochlear grooves of rabbit knees. The rabbits were randomly assigned into 3 groups: Apt19s-functionalized scaffold group, scaffold-only group, and control group. Animals were sacrificed at 6 and 12 weeks after transplantation. Repaired tissues were evaluated via gross examination, histologic examination, and immunohistochemistry. Results: In vitro, this aptamer-functionalized scaffold could recruit bone marrow–derived MSCs and support cell adhesion. In vivo, the aptamer-functionalized scaffold enhanced cell homing in comparison with the aptamer-free scaffold. The aptamer-functionalized scaffold group also exhibited superior cartilage restoration when compared with the scaffold-only group and the control group. Conclusion: The Apt19s-functionalized scaffold exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of cartilage repair than the scaffold only or control in an osteochondral defect model. Clinical Relevance: The findings demonstrate a promising strategy of using aptamer-functionalized bioscaffolds for restoration of chondral/osteochondral defects via aptamer-introduced homing of MSCs.

The role of growth factor in the repair of articular cartilage

2019 ◽  
Author(s):  
Yu Zhang ◽  
Zishu Chai ◽  
Chengqiang Yu ◽  
Youcai Wu ◽  
Yufu Ou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Repair ◽  
Research Progress ◽  
Articular Cartilage Repair ◽  
Synthetic Compounds ◽  
Inorganic Particles

Abstract Background: Natural degeneration or trauma of articular cartilage all can lead to its structural and functional damage. Because of its lack of blood supply and innervation, it has low metabolic activity and difficulty in self-repair after injury. Growth factors provide a new direction for the repair of articular cartilage damage and play an important role. This article will systematically summarize the research progress of traditional growth factors, mainly introduce the newly found growth factors and other synthetic compounds and inorganic particles that can induce stem cells to differentiate into cartilage.Methods: English literatures published in PubMed and SCI databases from August 2000 to August 2019 were searched, Review the relevant literature, The two authors evaluated and screened the quality of the literatures respectively, and senior authors further evaluated them to resolve the disagreement on the inclusion of literatures.Results: Growth factors can significantly promote stem cell proliferation and differentiation. A variety of growth factors can exert synergistically to promote the differentiation of stem cells into cartilage, so as to promote the regeneration of cartilage tissue and repair the damage of articular cartilage. Traditional growth factors that promote articular cartilage repair are bone morphogenetic proteins, cartilage derived morphogenetic protein, transcription growth factor β, fibroblast growth factors and insulin⁃like growth factors. Recent studies have found that kartogenin, platelet-rich plasma, platelet-rich fibrin, force growth factor, etc. can also effectively induce stem cells to differentiate into cartilage and maintain chondrocyte phenotype, synthetic compounds such as dexamethasone and some inorganic particles also promote chondrogenic differentiation.Conclusions: The newly discovered growth factors promote the development of articular cartilage repair, but its mechanism of action is not clear. There are no in vivo experimental studies on dexamethasone and inorganic particles, and its repairing effect and safety are for further study. The synergistic or antagonistic effects between different growth factors, the optimal concentration ratio, and the differences in in vivo and in vitro roles need further study. At present, the research on growth factors mostly stays at the basic stage, and there are few clinical studies, which will be an important direction for further research.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

Effects of in vitro low oxygen tension preconditioning of buccal fat pad stem cells on in Vivo articular cartilage tissue repair

Life Sciences ◽  
2021 ◽  
pp. 119728
Author(s):  
Fatemeh Dehghani Nazhvani ◽  
Leila Mohammadi Amirabad ◽  
Arezo Azari ◽  
Hamid Namazi ◽  
Simzar Hosseinzadeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Tissue Repair ◽  
Cartilage Tissue ◽  
Low Oxygen ◽  
Fat Pad ◽  
Buccal Fat Pad ◽  
Low Oxygen Tension

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.

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