scholarly journals Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model

2020 ◽  
Author(s):  
Tomoharu Takagi ◽  
Tamon Kabata ◽  
Katsuhiro Hayashi ◽  
Xiang Fang ◽  
Yoshitomo Kajino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Cruciate Ligament ◽  
Cell Sheet ◽  
Rabbit Model ◽  
Cartilage Degeneration ◽  
Left Knee ◽  
Control Group ◽  
Control Groups ◽  
Cell Sheets

Abstract Background: Subcutaneous adipose tissue represents an abundant source of multipotent adult stem cells named as Adipose-derived stem cells (ADSCs). With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model.Methods: Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically.Results: Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups.Conclusions: Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes.

scholarly journals Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomoharu Takagi ◽  
Tamon Kabata ◽  
Katsuhiro Hayashi ◽  
Xiang Fang ◽  
Yoshitomo Kajino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Cruciate Ligament ◽  
Cell Sheet ◽  
Rabbit Model ◽  
Cartilage Degeneration ◽  
Left Knee ◽  
Control Group ◽  
Control Groups ◽  
Cell Sheets

Abstract Background Subcutaneous adipose tissue represents an abundant source of multipotent adult stem cells named as Adipose-derived stem cells (ADSCs). With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model. Methods Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically. Results Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups. Conclusions Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes.

scholarly journals Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model

2020 ◽  
Author(s):  
Tomoharu Takagi ◽  
Tamon Kabata ◽  
Katsuhiro Hayashi ◽  
Xiang Fang ◽  
Yoshitomo Kajino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Cruciate Ligament ◽  
Cell Sheet ◽  
Rabbit Model ◽  
Cartilage Degeneration ◽  
Trophic Factors ◽  
Control Group ◽  
Control Groups ◽  
Cell Sheets

Abstract Background: Adipose-derived stem cells (ADSCs) represent an abundant source of multipotent adult stem cells easily isolated from subcutaneous adipose tissue. With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model. Methods: Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically. Results: Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups. Conclusions: Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes by secretion of trophic factors.

scholarly journals Stem cell application in rotator cuff repair: Interposition stem cell sheet versus overlaid stem cell sheet

2020 ◽  
Author(s):  
Jae hee Choi ◽  
Michael Seungcheol Kang ◽  
Myung Jin Shin ◽  
Dong Min Kim ◽  
Yu Na Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rotator Cuff ◽  
Rotator Cuff Repair ◽  
Surgical Repair ◽  
Cell Sheet ◽  
Biomechanical Analysis ◽  
Control Group ◽  
Cell Sheets ◽  
Cuff Repair

Abstract Background Stem cells are an effective method of biologic healing and can be used to enhance the natural enthesis of the tendon-to-bone junction in rotator cuff repair. The purpose of this study was to investigate if the application of engineered stem cell sheets using adipose-derived cells (ADSCs) was effective in regeneration of natural enthesis and if there was a difference in the result of repair depending on the applied location Methods A chronic rotator cuff tear model was induced for 2 weeks, and cell sheets made using ADSCs isolated from rats were transplanted into the tendon-to-bone junction during surgical repair. Depending on the transplant location of the cell sheet, the difference in rotator cuff healing level between the overlaid group and the interposition group was compared to the surgical repair only group. The samples were obtained based on the tendon-to-bone junction and analysis of gross morphology, histology staining, and biomechanical analysis were performed. Results The differentiation potentials of ADSCs as stem cells were confirmed, as was the potential for tenogenic differentiation by growth factors. ADSCs were prepared as a sheet form to maintain the shape at the target site and to be easily attached. GFP-expressing ADSCs were proliferated in vivo and observed at the transplantation site. The overall healing level was better in the cell sheet transplanted group than in the control group that surgical repair only. Additionally, differences in healing level were shown depending on the cell sheet location by morphological, histological, and biomechanical perspectives. Histological results showed that the interposition transplantation group (1.75 ± 0.43, P = 0.004) showed better fibrocartilage formation and collagen orientation at the junction than the overlaid transplantation group (0.86 ± 0.83). Conclusion In the chronic rotator cuff repair model, the engineered stem cell sheets enhanced the regeneration of the tendon-to-bone junction. This regeneration was more effective when the stem cell sheet was interpositioned at the tendon-to-bone interface. Trial registration: Not applicable

Construction of a Blood Vessel Wall with Adipose-Derived Stem Cell Sheets In Vitro

2021 ◽  
Vol 11 (8) ◽  
pp. 1452-1458
Author(s):  
Zhicheng Xu ◽  
Qun Zhang
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Adult Stem Cells ◽  
Transforming Growth Factor ◽  
Polyglycolic Acid ◽  
Large Vessel ◽  
Elastic Fibers ◽  
Control Group ◽  
Cell Sheets

Adipose-derived stem cells (ASCs) are a reliable and easily accessible source of adult stem cells. Thus, ASCs are increasingly used as seed cells in tissue engineering. This report investigated the possibility of engineering a large vessel using unwoven polyglycolic acid (PGA) fibers covered with ASC sheets treated with transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). After coiling around a silicone tube, the complex was secured by surgical sutures and cultured In Vitro for six weeks. Gross views showed that glossy and smooth tubular tissue was engineered. Histological examination revealed regularly distributed cells and a few collagenous and elastic fibers in the differentiated group. Cells were randomly distributed, and disorganized collagenous and small elastic fibers were detected in the control group. Our results indicate the promising potential of ASC sheets and PGA fibers for the construction of large vessel walls.

scholarly journals Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes

2018 ◽  
Vol 102 (4) ◽  
pp. 562-569 ◽  
Author(s):  
Jialin Chen ◽  
Wei Zhang ◽  
Ludvig J Backman ◽  
Peyman Kelk ◽  
Patrik Danielson
Keyword(s):  
Stem Cells ◽  
Mechanical Stimulation ◽  
Periodontal Ligament ◽  
Synergistic Effects ◽  
Mechanical Strain ◽  
Cell Sheet ◽  
Corneal Stroma ◽  
Cell Sheets ◽  
Periodontal Ligament Stem Cells ◽  
Gene And Protein Expression

AimsTo explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium.MethodsPDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining.ResultsDome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma.ConclusionDome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.

scholarly journals Disturbances in Metabolic Pathways and the Identification of a Potential Biomarker Panel for Early Cartilage Degeneration in a Rabbit Anterior Cruciate Ligament Transection Model

Cartilage ◽  
2020 ◽  
pp. 194760352092143
Author(s):  
Yiwen Hu ◽  
Qian Wu ◽  
Yang Qiao ◽  
Peng Zhang ◽  
Wentao Dai ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Pearson Correlation ◽  
Rabbit Model ◽  
Cartilage Degeneration ◽  
Anterior Cruciate Ligament Transection ◽  
Sham Surgery ◽  
Potential Biomarker ◽  
Anterior Cruciate ◽  
Potential Biomarkers

Objective This study aimed to assess the association between synovial fluid (SF) metabolites and magnetic resonance imaging (MRI) measurements of cartilage biochemical composition to identify potential SF biomarkers for detecting the early onset of cartilage degeneration in a rabbit model. Methods Both knees of 12 New Zealand White rabbits were used. The anterior cruciate ligament transection (ACLT) model was performed on right knees, and the sham surgery on left knees. MRI UTE-T2* scanning and SF sample collection were performed on ACLT knees at 4 and 8 weeks postsurgery and on sham surgery knees at 4 weeks postsurgery. Ultra-performance liquid chromatography–mass spectrometry and multivariate statistical analysis were used to distinguish samples in three groups. Pathway and receiver operating characteristic analyses were utilized to identify potential metabolite biomarkers. Results There were 12 knees in sham surgery models, 11 in ACLT models at 4 weeks postsurgery, and 10 in ACLT models at 8 weeks postsurgery. UTE-T2* values for the lateral tibia cartilage showed significant decreases over the study period. Levels of 103 identified metabolites in SF were markedly different among three groups. Furthermore, 24 metabolites were inversely correlated with UTE-T2* values of the lateral tibia cartilage, while hippuric acid was positively correlated with UTE-T2* values of the lateral tibia cartilage. Among 25 potential markers, N1-acetylspermidine, 2-amino-1,3,4-octadecanetriol, l-phenylalanine, 5-hydroxy-l-tryptophan, and l-tryptophan were identified as potential biomarkers with high area under the curve values and Pearson correlation coefficients. Conclusion Five differential metabolites in SF were found as potential biomarkers for the early detection of cartilage degeneration in the rabbit ACLT model.

scholarly journals A Preliminary Study Comparing Microfracture and Local Adherent Transplantation of Autologous Adipose-Derived Stem Cells Followed by Intraarticular Injection of Platelet-Rich Plasma for the Treatment of Chondral Defects in Rabbits

Cartilage ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 410-416 ◽  
Author(s):  
Timea Spakova ◽  
Judita Amrichova ◽  
Jana Plsikova ◽  
Denisa Harvanova ◽  
Slavomir Hornak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cartilage Defect ◽  
Platelet Rich Plasma ◽  
Femoral Condyle ◽  
Rabbit Model ◽  
Intraarticular Injection ◽  
Control Group ◽  
Adipose Derived Stem Cells ◽  
Group 2 ◽  
Group 1

Objective This study aimed to compare microfracture and application of adipose-derived stem cells (ADSCs) by local adherent technique enhanced by platelet-rich plasma (PRP) to provide a new approach for the repair of cartilage defect. Design Full-thickness cylindrical defects were created in the medial femoral condyle in 9 New Zealand White rabbits (5 months old, 4.65 ± 0.20 kg). Two groups of rabbits ( n = 3) were either treated with ADSCs (Group 1) or the microfracture technique (Group 2) following intraarticular injection of PRP 3 times in weekly intervals. Rabbits in control group ( n = 3) remained untreated. The outcome was assessed macroscopically, histologically, and immunohistochemically. Results At the end of week 12, Group 1 showed better defect filling compared with Group 2. Specimens treated with the combination of ADSCs and PRP exhibited significant differences from the other groups in all criteria of International Cartilage Repair Society macroscopic scoring system. Conclusions Intraarticular injection of autologous PRP in combination with transplantation of autologous ADSCs by local adherent technique enhances the quality of cartilage defect repair with better results in comparison with microfracture surgery in a rabbit model.

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