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 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.

Repair of Osteochondral Defects With Predifferentiated Mesenchymal Stem Cells of Distinct Phenotypic Character Derived From a Nanotopographic Platform

2020 ◽  
Vol 48 (7) ◽  
pp. 1735-1747
Author(s):  
Yingnan Wu ◽  
Zheng Yang ◽  
Vinitha Denslin ◽  
XiaFei Ren ◽  
Chang Sheng Lee ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Defect Site

Background: Articular cartilage has a zonal architecture and biphasic mechanical properties. The recapitulation of surface lubrication properties with high compressibility of the deeper layers of articular cartilage during regeneration is essential in achieving long-term cartilage integrity. Current clinical approaches for cartilage repair, especially with the use of mesenchymal stem cells (MSCs), have yet to restore the hierarchically organized architecture of articular cartilage. Hypothesis: MSCs predifferentiated on surfaces with specific nanotopographic patterns can provide phenotypically stable and defined chondrogenic cells and, when delivered as a bilayered stratified construct at the cartilage defect site, will facilitate the formation of functionally superior cartilage tissue in vivo. Study Design: Controlled laboratory study. Methods: MSCs were subjected to chondrogenic differentiation on specific nanopatterned surfaces. The phenotype of the differentiated cells was assessed by the expression of cartilage markers. The ability of the 2-dimensional nanopattern-generated chondrogenic cells to retain their phenotypic characteristics after removal from the patterned surface was tested by subjecting the enzymatically harvested cells to 3-dimensional fibrin hydrogel culture. The in vivo efficacy in cartilage repair was demonstrated in an osteochondral rabbit defect model. Repair by bilayered construct with specific nanopattern predifferentiated cells was compared with implantation with cell-free fibrin hydrogel, undifferentiated MSCs, and mixed-phenotype nanopattern predifferentiated MSCs. Cartilage repair was evaluated at 12 weeks after implantation. Results: Three weeks of predifferentiation on 2-dimensional nanotopographic patterns was able to generate phenotypically stable chondrogenic cells. Implantation of nanopatterned differentiated MSCs as stratified bilayered hydrogel constructs improved the repair quality of cartilage defects, as indicated by histological scoring, mechanical properties, and polarized microscopy analysis. Conclusion: Our results indicate that with an appropriate period of differentiation, 2-dimensional nanotopographic patterns can be employed to generate phenotypically stable chondrogenic cells, which, when implanted as stratified bilayered hydrogel constructs, were able to form functionally superior cartilage tissue. Clinical Relevance: Our approach provides a relatively straightforward method of obtaining large quantities of zone-specific chondrocytes from MSCs to engineer a stratified cartilage construct that could recapitulate the zonal architecture of hyaline cartilage, and it represents a significant improvement in current MSC-based cartilage regeneration.

scholarly journals Exosomes from Kartogenin-Pretreated Infrapatellar Fat Pad Mesenchymal Stem Cells Enhance Chondrocyte Anabolism and Articular Cartilage Regeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jiahua Shao ◽  
Jun Zhu ◽  
Yi Chen ◽  
Qiwei Fu ◽  
Lexiang Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Regeneration ◽  
Infrapatellar Fat Pad ◽  
Cartilage Defects ◽  
Control Group ◽  
Fat Pad ◽  
And Control

Objective. To evaluate the effect of Kartogenin-pretreated exosomes derived from infrapatellar fat pad mesenchymal stem cells on chondrocyte in vitro and articular cartilage regeneration in vivo. Methods. Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were isolated from rabbits to harvest exosomes. After identification of mesenchymal stem cells and exosomes, rabbit chondrocytes were divided into three groups for further treatment: the EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells), KGN-EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN), and control group. After processing and proliferation, phenotypic changes of chondrocytes were measured. In the in vivo study, 4 groups of rabbits with articular cartilage injury were treated with KGN-EXO, EXO, IPFP-MSCs, and control. Macroscopic evaluation and histological evaluation were made to figure out the different effects of the 4 groups on cartilage regeneration in vivo. Results. The proliferation rate of chondrocytes in the EXO or KGN-EXO group was significantly higher than that in the control group ( P < 0.05 ). The qRT-PCR results showed that the expression of Sox-9, Aggrecan, and Col II was the highest in the KGN-EXO group compared with the EXO group and the control group ( P < 0.05 ). The results of Western blot were consistent with the results of qRT-PCR. In vivo, the cartilage defects in the KGN-EXO group showed better gross appearance and improved histological score than those in IPFP-MSC groups, EXO groups, and control groups ( P < 0.05 ). At 12 weeks, the defect site in the KGN-EXO group was almost completely repaired with a flat and smooth surface, while a large amount of hyaline cartilage-like structures and no obvious cracks were observed. Conclusion. Our study demonstrates that the exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN have potent ability to induce chondrogenic differentiation of stem cells, effectively promoting the proliferation and the expression of chondrogenic proteins and genes of chondrocytes. The KGN-EXO can also promote the repair of articular cartilage defects more effectively, which can be used as a potential therapeutic method in the future.

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 Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Francesco Perdisa ◽  
Natalia Gostyńska ◽  
Alice Roffi ◽  
Giuseppe Filardo ◽  
Maurilio Marcacci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Clinical Evidence ◽  
Cartilage Regeneration ◽  
Therapeutic Approaches ◽  
Differentiated Cells ◽  
Cartilage Disease

Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs) provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs) are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview ofin vivostudies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

scholarly journals A Bioactive Cartilage Graft of IGF1-Transduced Adipose Mesenchymal Stem Cells Embedded in an Alginate/Bovine Cartilage Matrix Tridimensional Scaffold

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Nidia K. Moncada-Saucedo ◽  
Iván A. Marino-Martínez ◽  
Jorge Lara-Arias ◽  
Víktor J. Romero-Díaz ◽  
Alberto Camacho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
De Novo ◽  
Cartilage Regeneration ◽  
Cartilage Injuries ◽  
Physicochemical Features ◽  
Microenvironmental Factors ◽  
Articular Cartilage Injuries

Articular cartilage injuries remain as a therapeutic challenge due to the limited regeneration potential of this tissue. Cartilage engineering grafts combining chondrogenic cells, scaffold materials, and microenvironmental factors are emerging as promissory alternatives. The design of an adequate scaffold resembling the physicochemical features of natural cartilage and able to support chondrogenesis in the implants is a crucial topic to solve. This study reports the development of an implant constructed with IGF1-transduced adipose-derived mesenchymal stem cells (immunophenotypes: CD105+, CD90+, CD73+, CD14-, and CD34-) embedded in a scaffold composed of a mix of alginate/milled bovine decellularized knee material which was cultivated in vitro for 28 days (3CI). Histological analyses demonstrated the distribution into isogenous groups of chondrocytes surrounded by a de novo dense extracellular matrix with balanced proportions of collagens II and I and high amounts of sulfated proteoglycans which also evidenced adequate cell proliferation and differentiation. This graft also shoved mechanical properties resembling the natural knee cartilage. A modified Bern/O’Driscoll scale showed that the 3CI implants had a significantly higher score than the 2CI implants lacking cells transduced with IGF1 (16/18 vs. 14/18), representing high-quality engineering cartilage suitable for in vivo tests. This study suggests that this graft resembles several features of typical hyaline cartilage and will be promissory for preclinical studies for cartilage regeneration.

scholarly journals Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors

2020 ◽  
Vol 21 (6) ◽  
pp. 1967 ◽  
Author(s):  
Jae-Sung Ryu ◽  
Sang Young Seo ◽  
Eun-Jeong Jeong ◽  
Jong-Yeup Kim ◽  
Yong-Gon Koh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Cartilage Regeneration ◽  
Ganglioside Gm3

Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.

scholarly journals Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

2014 ◽  
Vol 2 ◽  
Author(s):  
Vyacheslav Ogay ◽  
Miras Karzhauov ◽  
Ainur Mukhambetova ◽  
Eric Raimagambetov ◽  
Nurlan Batpenov
Keyword(s):  
Stem Cells ◽  
Molecular Weight ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Cartilage Defect ◽  
Femoral Condyle ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Low Molecular Weight ◽  
Defect Area

Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs) with low molecular weight hyaluronic acid (HA) could promote regeneration of massive cartilage in rabbits.Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek). The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml) were suspended in 0.5% low molecular weight HA (0.15 ml) and injected into the left knee, and HA solution (0.30 ml) alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days.Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage.Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

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