scholarly journals Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage

2021 ◽  
Vol 9 ◽  
Author(s):  
Isabele Camargo Brindo da Cruz ◽  
Ana Paula Pereira Velosa ◽  
Solange Carrasco ◽  
Antonio dos Santos Filho ◽  
Jurandir Tomaz de Miranda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Fas Ligand ◽  
Cartilage Regeneration ◽  
Type Ii Collagen ◽  
Adipose Derived Stem Cells ◽  
Type V ◽  
Rabbit Articular Cartilage

Collagen is essential for cartilage adhesion and formation. In the present study, histology, immunofluorescence, morphometry, and qRT-PCR suggested that adipose-derived stem cells (ADSCs) stimulated by type V collagen (Col V) induce a significant increase of type II collagen (Col II) in the degenerative area of surgical-induced osteoarthritic rabbit articular cartilage (OA). In vitro, the effects of Col V on the proliferation and differentiation of ADSC were investigated. The expression of the cartilage-related genes Col2a1 and Acan was significantly upregulated and Pou5fl was downregulated post-ADSC/Col V treatment. Post-ADSC/Col V treatment, in vivo analyses revealed that rabbits showed typical signs of osteoarthritic articular cartilage regeneration by hematoxylin and eosin (H&E) and Safranin O/Fast Green staining. Immunohistochemical staining demonstrated that the volume of Col II fibers and the expression of Col II protein were significantly increased, and apoptosis Fas ligand positive significantly decreased post-ADSC/Col V treatment. In conclusion, the expression of Col II was higher in rabbits with surgical-induced osteoarthritic articular cartilage; hence, ADSC/Col V may be a promising therapeutic target for OA treatment.

scholarly journals Method for in vitro production of cartilage microtissues from scaffold-free spheroids composed of human adipose-derived stem cells

2020 ◽  
Vol 7 (4) ◽  
pp. 3697-3708
Author(s):  
Vy Thi-Kieu Tu ◽  
Ha Thi-Ngan Le ◽  
Xuan Hoang-Viet To ◽  
Phuc Dang-Ngoc Nguyen ◽  
Phat Duc Huynh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cartilage Damage ◽  
Cartilage Regeneration ◽  
Type Ii Collagen ◽  
Adipose Derived Stem Cells ◽  
Type Ii ◽  
In Vitro Production ◽  
Engineered Cartilage

Introduction: Cartilage damage is one of the injuries that is difficult for the human body to self-repair due to the avascular and completely mature tissue with only few stem or progenitor cells present. Recently, some studies showed that engineered cartilage tissues could be used to treat or improve this injury. This study aimed to produce the cartilage microtissues from the differentiation of scaffold-free spheroids composed of human adipose-derived stem cells. Methods: Human adipose-derived stem cells (ADSCs) were isolated and expanded following the previously published study. They were then cultured in the non-adherent condition to produce spheroids. The spheroids of the ADSCs were collected and induced into cartilage microtissues in the inducible medium for 21 days. The cartilage microtissue was characterized by some cartilage phenotype markers, including the accumulation of extracellular matrix proteins (aggrecan, glycosaminoglycan, and type II collagen), and the expression of certain genes specific to chondrocytes (Sox9, Col2, Col1, and Acan). Results: The results showed that the expression of chondrocyte-specific genes gradually increased during the 21 days of culture for differentiation. On day 21, the microtissues expressed aggrecan, glycosaminoglycan, and type II collagen proteins. Conclusion: This study demonstrated that cartilage microtissues could easily be produced from scaffold-free spheroids from ADSCs. Thus, cartilage microtissues can be produced in this manner for in vivo transplantation to promote cartilage regeneration, or to produce cartilage tissues for in vitro studies.  

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.

scholarly journals Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9

2020 ◽  
Vol 52 (4) ◽  
pp. 672-681 ◽  
Author(s):  
Jiyun Lee ◽  
Chang Youn Lee ◽  
Jun-Hee Park ◽  
Hyang-Hee Seo ◽  
Sunhye Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Cartilage Regeneration ◽  
Hypertrophic Chondrocytes ◽  
Joint Disease ◽  
Chondrocyte Differentiation ◽  
Adipose Derived Stem Cells ◽  
Key Factor

Abstract Osteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage and the underlying bone. Because cartilage and chondrocytes lack the ability to self-regenerate, efforts have been made to utilize stem cells to treat OA. Although various methods have been used to differentiate stem cells into functional chondrocytes, the currently available methods cannot induce stem cells to undergo differentiation into chondrocyte-like cells without inducing characteristics of hypertrophic chondrocytes, which finally lead to cartilage disintegration and calcification. Therefore, an optimized method to differentiate stem cells into chondrocytes that do not display undesired phenotypes is needed. This study focused on differentiating adipose-derived stem cells (ASCs) into functional chondrocytes using a small molecule that regulated the expression of Sox9 as a key factor in cartilage development and then explored its ability to treat OA. We selected ellipticine (ELPC), which induces chondrocyte differentiation of ASCs, using a GFP-Sox9 promoter vector screening system. An in vivo study was performed to confirm the recovery rate of cartilage regeneration with ASC differentiation into chondrocytes by ELPC in a collagenase-induced animal model of OA. Taken together, these data indicate that ellipticine induces ASCs to differentiate into mature chondrocytes without hypertrophic chondrocytes in vitro and in vivo, thus overcoming a problem encountered in previous studies. These results indicate that ELPC is a novel chondrocyte differentiation-inducing drug that shows potential as a cell therapy for OA.

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 In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Manuel Mata ◽  
Lara Milian ◽  
Maria Oliver ◽  
Javier Zurriaga ◽  
Maria Sancho-Tello ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Dental Pulp ◽  
Cartilage Regeneration ◽  
Cell Types ◽  
Dental Pulp Stem Cells ◽  
The Poor ◽  
Human Dental Pulp

Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs) to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

scholarly journals The Complexity of Joint Regeneration: How an Advanced Implant could Fail by Its In Vivo Proven Bone Component

10.36850/e3 ◽  
2021 ◽  
Author(s):  
Paweena Diloksumpan ◽  
Florencia Abinzano ◽  
Mylène de Ruijter ◽  
Anneloes Mensinga ◽  
Saskia Plomp ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Damage ◽  
Clinical Signs ◽  
Cartilage Regeneration ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Micro Computed Tomography ◽  
Bone Anchor

Articular cartilage damage is a major challenge in healthcare due to the lack of long-term repair options. There are several promising regenerative implant-based approaches for the treatment, but the fixation of the implant remains a significant challenge. This study evaluated the potential for repair of an osteochondral implant produced through a novel combined bioprinting-based chondral-bone integration, with and without cells, in an equine model. Implants consisted of a melt electrowritten polycaprolactone (PCL) framework for the chondral compartment, which was firmly integrated with a bone anchor. The bone anchor was produced by extrusion-based printing of a low-temperature setting bioceramic material that had been proven to be effective for osteo-regeneration in an orthotopic, non-load bearing and non-articular site in the same species in an earlier in vivo study. Articular cartilage-derived progenitor cells were seeded into the PCL framework and cultured for 28 days in vitro in the presence of bone morphogenetic protein-9 (BMP-9), resulting in the formation of abundant extracellular matrix rich in glycosaminoglycans (GAGs) and type II collagen. The constructs were implanted in the stifle joints of Shetland ponies with cell-free scaffolds as controls. Clinical signs were monitored, and progression of healing was observed non-invasively through radiographic examinations and quantitative gait analysis. Biochemical and histological analyses 6 months after implantation revealed minimal deposition of GAGs and type II collagen in the chondral compartment of the defect site for both types of implants. Quantitative micro-computed tomography showed collapse of the bone anchor with low volume of mineralized neo-bone formation in both groups. Histology confirmed that the PCL framework within the chondral compartment was still present. It was concluded that the collapse of the osteal anchor, resulting in loss of the mechanical support of the chondral compartment, strongly affected overall outcome, precluding evaluation of the influence of BMP-9 stimulated cells on in vivo cartilage regeneration.

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