scholarly journals BM-MSCs differentiated to chondrocytes for treatment of full-thickness cartilage defect of the knee

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Rodrigo Mardones ◽  
Alessio Giai Via ◽  
Gennaro Pipino ◽  
Claudio M. Jofre ◽  
Sara Muñoz ◽  
...  

Abstract Background Full-thickness articular cartilage injury of the knee is a major cause of disability. The aim of this study is to assess the outcome of patients treated with differentiated to chondrocytes bone marrow mesenchymal stem cells (BM-MSCs) cultured on a collagen type I/III (Chondro-Gide®) scaffold. The secondary aim was to confirm the absence of adverse events. Methods Fifteen patients (19 knees) with symptomatic full-thickness cartilage defects of the knee were enrolled. Bone marrow was harvested from the iliac crest, BM-MSCs were prepared, and expanded cells were grown in a standard medium or in a standard culture medium containing TGF-β. BM-MSCs differentiated to chondrocytes were seeded in a porcine collagen type I/III scaffold (Chondro-Gide®) and cultured in TGF-β containing media. After 4 weeks, the membrane was sutured on the cartilage defect. All patients underwent plain radiographs (antero-posterior, lateral, and axial view of the patella) and MRI of the affected knee. The Oxford knee score, the Lyhsolm scale, and the VAS score were administered to all patients. At final follow-up a MRI for the study of articular cartilage was undertaken. Results The mean size of the cartilage lesions was 20 × 17 mm (range, 15 × 10 mm–30 × 30 mm). At final follow-up, the median Oxford knee score and Lyhsolm scale scores significantly improved from 29 (range 12–39; SD 7.39) to 45 (range 24–48; SD 5.6) and from 55.5 (range 25–81; SD 17.7) to 94.5 (58–100; SD 10.8), respectively. Pain, according to the VAS score, significantly improved. Sixty percent of patients reported their satisfaction as excellent, 20% as good, 14% as fair, and 1 patient as poor. Conclusion The treatment of full-thickness chondral injuries of the knee with differentiated to chondrocytes BM-MSCs and Chondro-Gide® scaffold showed encouraging outcomes. Further studies involving more patients, and with longer follow-up, are required to evaluate the effectiveness of the treatment and the long-term results.

2020 ◽  
Author(s):  
Rodrigo Mardones ◽  
Alessio Giai Via ◽  
Gennaro Pipino ◽  
Claudio Jofrè ◽  
Sara Muñoz ◽  
...  

Abstract Background Full-thickness articular cartilage injury of the knee is a major cause of disability. The aim of this study is to assess the results of patients treated with differentiated to chondrocytes bone marrow Mesenchymal Stem Cells (BM-MSCs) cultured on a collagen Type I/III (Chondro-Gide®) scaffold. The secondary aim was to confirm the absence of adverse events. Methods Fifteen patients (19 knees) with symptomatic full-thickness cartilage defects of the knee have been enrolled for the study. Bone marrow was harvested from the iliac crest, BM-MSCs were prepared, and expanded cells were grown in a standard medium or in a standard culture medium containing TGF-β. BM-MSCs differentiated to chondrocytes were seeded in a porcine collagen Type I/III scaffold (Chondro-Gide®), and cultured in TGF- β containing media. After 4 weeks, the membrane was sutured on the cartilage defect. All patients underwent plain radiographs of the knee (antero-posterior, lateral, and axial view of the patella), and MRI of the affected knee. The Oxford knee score, the Lyhsolm scale, and the VAS score were administered to all patients. At final follow-up a MRI for the study of articular cartilage was undertaken. Results The mean size of the cartilage lesions was 20 × 17 mm (range, 15 × 10 mm − 30 × 30 mm). At final follow-up, the median Oxford knee score and Lyhsolm scale scores significantly improved from 29 (range 12–39; SD 7,39) to 45 (range 24–48; SD 5,6) and from 55.5 (range 25–81; SD 17,7) to 94.5 (58–100; SD 10,8) respectively. Pain, according the VAS score, significantly improved. 60% of patients reported their satisfaction as excellent, 20% as good, 14% as fair, and 1 patient as poor. Conclusion The treatment of full-thickness chondral injuries of the knee with differentiated to chondrocytes BM-MSCs and Chondro-Gide® scaffold showed encouraging outcomes. Further studies involving more patients, and with longer follow-up, are required in order to evaluate the effectiveness of the treatment and the long-term results.


2016 ◽  
Vol 38 (1) ◽  
pp. 319-329 ◽  
Author(s):  
Yulei Gao ◽  
Yinquan Zhang ◽  
Yanghu Lu ◽  
Yi Wang ◽  
Xingrui Kou ◽  
...  

Background/Aims: This study investigated the effect of silencing TOB1 (Transducer of ERBB2, 1) expression in bone marrow-derived mesenchymal stem cells (MSCs) on MSC-facilitated tendon-bone healing in a rat supraspinatus repair model. Methods: Rat MSCs were transduced with a recombinant lentivirus encoding short hairpin RNA (shRNA) against TOB1. MSC cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The effect of MSCs with TOB1 deficiency on tendon-bone healing in a rat rotator cuff repair model was evaluated by biomechanical testing, histological analysis and collagen type I and II gene expression. An upstream regulator (miR-218) of TOB1 was determined in MSCs. Results: We found that knockdown of TOB1 significantly increased the proliferative activity of rat MSCs in vitro. When MSCs with TOB1 deficiency were injected into injured rat supraspinatus tendon-bone junctions, the effect on tendon-bone healing was enhanced compared to treatment with control MSCs with normal TOB1 expression, as evidenced by elevated levels of ultimate load to failure and stiffness, increased amount of fibrocartilage and augmented expression of collagen type I and type II genes. In addition, we found that the TOB1 3′ untranslated region is a direct target of miR-218. Similar to the effect of TOB1 deficiency, overexpression of miR-218 effectively promoted tendon-bone healing in rat. Conclusion: These results suggest that TOB1 may play a negative role in the effect of MSCs on tendon-bone healing, and imply that expression of TOB1 may be regulated by miR-218.


2020 ◽  
Vol 21 (24) ◽  
pp. 9726
Author(s):  
Sandra Gromolak ◽  
Agnieszka Krawczenko ◽  
Agnieszka Antończyk ◽  
Krzysztof Buczak ◽  
Zdzisław Kiełbowicz ◽  
...  

Cell-based therapies using mesenchymal stem cells (MSCs) are a promising tool in bone tissue engineering. Bone regeneration with MSCs involves a series of molecular processes leading to the activation of the osteoinductive cascade supported by bioactive factors, including fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2). In this study, we examined the biological characteristics and osteogenic differentiation potential of sheep bone marrow MSCs (BM-MSCs) treated with 20 ng/mL of FGF-2 and 100 ng/mL BMP-2 in vitro. The biological properties of osteogenic-induced BM-MSCs were investigated by assessing their morphology, proliferation, phenotype, and cytokine secretory profile. The osteogenic differentiation was characterized by Alizarin Red S staining, immunofluorescent staining of osteocalcin and collagen type I, and expression levels of genetic markers of osteogenesis. The results demonstrated that BM-MSCs treated with FGF-2 and BMP-2 maintained their primary MSC properties and improved their osteogenic differentiation capacity, as confirmed by increased expression of osteocalcin and collagen type I and upregulation of osteogenic-related gene markers BMP-2, Runx2, osterix, collagen type I, osteocalcin, and osteopontin. Furthermore, sheep BM-MSCs produced a variety of bioactive factors involved in osteogenesis, and supplementation of the culture medium with FGF-2 and BMP-2 affected the secretome profile of the cells. The results suggest that sheep osteogenic-induced BM-MSCs may be used as a cellular therapy to study bone repair in the preclinical large animal model.


2021 ◽  
Vol 22 (24) ◽  
pp. 13458
Author(s):  
Ragda Saleem ◽  
Samih Mohamed-Ahmed ◽  
Rammah Elnour ◽  
Ellen Berggreen ◽  
Kamal Mustafa ◽  
...  

Oxidative stress from high levels of intracellular reactive oxygen species (ROS) has been linked to various bone diseases. Previous studies indicate that mesenchymal stem cells (MSC) secrete bioactive factors (conditioned medium (MSC-CM)) that have antioxidant effects. However, the antioxidant role of MSC-CM on osteogenesis has not been fully studied. We aimed to identify antioxidant proteins in MSC-CM using mass spectrometry-based proteomics and to explore their effects on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSC) exposed to oxidative stress induced by hydrogen peroxide (H2O2). Our analysis revealed that MSC-CM is comprised of antioxidant proteins that are involved in several biological processes, including negative regulation of apoptosis and positive regulation of cell proliferation. Then, hBMSC exposed to H2O2 were treated with MSC-CM, and the effects on their osteogenic differentiation were evaluated. MSC-CM restored H2O2-induced damage to hBMSC by increasing the antioxidant enzyme-SOD production and the mRNA expression level of the anti-apoptotic BCL-2. A decrease in ROS production and cellular apoptosis was also shown. MSC-CM also modulated mRNA expression levels of osteogenesis-related genes, runt-related transcription factor 2, collagen type I, bone morphogenic protein 2, and osteopontin. Furthermore, collagen type I protein secretion, alkaline phosphatase activity, and in vitro mineralization were increased. These results indicate that MSC-CM contains several proteins with antioxidant and anti-apoptotic properties that restored the impaired hBMSC osteogenic differentiation associated with oxidative stress.


2016 ◽  
Vol 17 (10) ◽  
pp. 3145-3152 ◽  
Author(s):  
Nelda Vázquez-Portalatı́n ◽  
Claire E. Kilmer ◽  
Alyssa Panitch ◽  
Julie C. Liu

2016 ◽  
Vol 130 (7) ◽  
pp. 650-655 ◽  
Author(s):  
K Sato ◽  
S Chitose ◽  
T Kurita ◽  
H Umeno

AbstractBackground:There is growing evidence to suggest that cells in the maculae flavae are tissue stem cells of the human vocal fold and maculae flavae are a stem cell niche.Methods:Three newborn vocal folds were investigated. Immunoreactivity to antibodies directed to cytokeratin, desmin, glial fibrillary acidic protein, vimentin, cluster of differentiation 34, cluster of differentiation 45, collagen type I, telomerase reverse transcriptase, SOX17 and stage-specific embryonic antigen 3 was investigated.Results:The cells in the newborn maculae flavae expressed haematopoietic markers (cluster of differentiation 34, cluster of differentiation 45) and collagen type I, which are the major makers of bone marrow derived circulating fibrocytes. The cells expressed epithelium, muscle, neural and mesenchymal cell associated proteins, and endodermal marker, indicating that they are undifferentiated and express proteins of all three germ layers. The cells also expressed stage-specific embryonic antigen 3 and telomerase reverse transcriptase.Conclusion:The cells in the newborn maculae flavae are undifferentiated cells arising from the differentiation of bone marrow cells. The results of this study are consistent with the hypothesis that the cells in maculae flavae are tissue stem cells.


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