scholarly journals Could the Enrichment of a Biomaterial with Conditioned Medium or Extracellular Vesicles Modify Bone-Remodeling Kinetics during a Defect Healing? Evaluations on Rat Calvaria with Synchrotron-Based Microtomography

2020 ◽  
Vol 10 (7) ◽  
pp. 2336
Author(s):  
Alessandra Giuliani ◽  
Gabriela Sena ◽  
Giuliana Tromba ◽  
Emanuela Mazzon ◽  
Antonella Fontana ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Conditioned Medium ◽  
Bone Remodeling ◽  
Extracellular Vesicles ◽  
Bone Tissue Regeneration ◽  
Bone Mass Density ◽  
Defect Healing ◽  
Defect Site

Tissue engineering has been shown to offer promising approaches for bone regeneration, mostly based on replacement with biomaterials that provide specific environments and support for bone growth. In this context, we previously showed that mesenchymal stem cells (MSCs) and their derivatives, such as conditioned medium (CM) and extracellular vesicles (EV), when seeded on collagen membranes (COL) or polylactide (PLA) biomaterials, are able to favor bone tissue regeneration, especially evidenced in animal model calvary defects. In the present study, we investigated whether the enrichment of a rat calvary defect site with CM, EVs and polyethylenimine (PEI)-engineered EVs could substantially modify the bone remodeling kinetics during defect healing, as these products were reported to favor bone regeneration. In particular, we focused the study, performed by synchrotron radiation-based high-resolution tomography, on the analysis of the bone mass density distribution. We proved that the enrichment of a defect site with CM, EVs and PEI-EVs substantially modifies, often accelerating, bone remodeling kinetics and the related mineralization process during defect healing. Moreover, different biomaterials (COL or PLA) in combination with stem cells of different origin (namely, human periodontal ligament stem cells-hPDLSCs and human gingival mesenchymal stem cells-hGMSCs) and their own CM, EVs and PEI-EVs products were shown to exhibit different mineralization kinetics.

scholarly journals A New Polycaprolactone-Based Biomembrane Functionalized with BMP-2 and Stem Cells Improves Maxillary Bone Regeneration

Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1774
Author(s):  
Céline Stutz ◽  
Marion Strub ◽  
François Clauss ◽  
Olivier Huck ◽  
Georg Schulz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Remodeling ◽  
New Technology ◽  
Bone Lesion ◽  
Oral Diseases ◽  
Maxillary Bone

Oral diseases have an impact on the general condition and quality of life of patients. After a dento-alveolar trauma, a tooth extraction, or, in the case of some genetic skeletal diseases, a maxillary bone defect, can be observed, leading to the impossibility of placing a dental implant for the restoration of masticatory function. Recently, bone neoformation was demonstrated after in vivo implantation of polycaprolactone (PCL) biomembranes functionalized with bone morphogenic protein 2 (BMP-2) and ibuprofen in a mouse maxillary bone lesion. In the present study, human bone marrow derived mesenchymal stem cells (hBM-MSCs) were added on BMP-2 functionalized PCL biomembranes and implanted in a maxillary bone lesion. Viability of hBM-MSCs on the biomembranes has been observed using the “LIVE/DEAD” viability test and scanning electron microscopy (SEM). Maxillary bone regeneration was observed for periods ranging from 90 to 150 days after implantation. Various imaging methods (histology, micro-CT) have demonstrated bone remodeling and filling of the lesion by neoformed bone tissue. The presence of mesenchymal stem cells and BMP-2 allows the acceleration of the bone remodeling process. These results are encouraging for the effectiveness and the clinical use of this new technology combining growth factors and mesenchymal stem cells derived from bone marrow in a bioresorbable membrane.

scholarly journals Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Miguel Tofiño-Vian ◽  
Maria Isabel Guillén ◽  
María Dolores Pérez del Caz ◽  
Miguel Angel Castejón ◽  
Maria José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Relevant Factor ◽  
Paracrine Effects ◽  
Inflammatory Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL-) 1βindicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associatedβ-galactosidase activity and the accumulation ofγH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

Bone mesenchymal stem cells derived extracellular vesicles promotes TRAIL-related apoptosis of hepatocellular carcinoma cells via the delivery of microRNA-20a-3p

2020 ◽  
pp. 1-13
Author(s):  
Lu Deng ◽  
Chang Wang ◽  
Chao He ◽  
Li Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Cell Apoptosis ◽  
Bone Mesenchymal Stem Cells ◽  
Hcc Cells

OBJECTIVE: Bone mesenchymal stem cells (BMSCs) have been widely researched in cancer treatment, including hepatocellular carcinoma (HCC). This study intended to discuss the mechanism of miR-20a-3p in BMSCs-extracellular vesicles (EVs) in HCC apoptosis. METHODS: BMSCs were isolated and identified. EVs derived from BMSCs were extracted and identified. After overexpressing or inhibiting miR-20a-3p expression in BMSCs, EVs were extracted and acted on HCC cells and transplanted tumors. HCC cell apoptosis in the treatment of BMSCs-conditioned medium, BMSCs-EVs and/or miR-20a-3p mimic/inhibitor were evaluated, with the detection of levels of TRAIL and TRAIL-related proteins. A functional rescue experiment about c-FLIP was carried out in HCC cells. The target binding relationship between miR-20a-3p and c-FLIP was detected. The subcutaneous tumorigenesis model of mice was established and injected with BMSCs-EVs to estimate the effect of BMSCs-EVs-miR-20a-3p on HCC growth. RESULTS: EVs isolated from BMSCs conditioned medium promoted the apoptosis of HCC cells. After BMSCs-EVs treatment, TRAIL levels, downstream proteins and miR-20a-3p were increased significantly, but the expression of c-FLIP was decreased. miR-20a-3p could target c-FLIP. BMSCs-EVs inhibited the growth of HCC cells, decreased c-FLIP expression, increased TRAIL levels, and promote the of HCC cell apoptosis. BMSCs-EVs with overexpressing miR-20a-3p further enhanced the apoptotic effect of HCC cells in vitro and in vivo. CONCLUSION: BMSCs-EVs-carried miR-20a-3p targets c-FLIP and increases TRAIL levels in HCC cells, thus promoting TRAIL-related apoptosis.

scholarly journals A defined mix of cytokines mimics conditioned medium from cultures of bone marrow-derived mesenchymal stem cells and elicits bone regeneration

2017 ◽  
Vol 50 (3) ◽  
pp. e12333 ◽  
Author(s):  
Wataru Katagiri ◽  
Kohei Sakaguchi ◽  
Takamasa Kawai ◽  
Yukiko Wakayama ◽  
Masashi Osugi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Conditioned Medium

scholarly journals Bone-targeted extracellular vesicles from mesenchymal stem cells for osteoporosis therapy

2020 ◽  
Author(s):  
Yayu Wang ◽  
Jie Yao ◽  
Lizhao Cai ◽  
Tong Liu ◽  
Xiaogang Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Bone Regeneration ◽  
Click Chemistry ◽  
Extracellular Vesicles ◽  
Osteoporosis Therapy ◽  
High Affinity ◽  
Bone Targeting

Abstract Background Osteoporosis (OP) is one of the most common chronic diseases, but the drugs used to treat OP have strong side effects. Recently, bone regeneration in stem cell derivatives represented by extracellular vesicles (EVs) has provided a new strategy for the prevention and treatment of OP. EVs derived from mouse mesenchymal stem cells (mMSCs) have a positive effect on bone regeneration, yet their clinical application has been hampered by the lack of bone-targeting. Alendronate (Ale) has a specifically affinity for bone tissue through a high affinity with hydroxyapatite. Herein, we used copper-free "click chemistry” to combine EVs with Ale together for OP targeted therapy. Bone targeting was facilitated via Ale binding to hydroxyapatite, which is highly expressed on the bone surface. Methods In vitro, bone targeting of Ale-EVs was confirmed by flow cytometry. Also, Ex vivo fluorescent imaging data revealed strong fluorescent signals in bone tissues in mice treated with Ale-EVs-DiD compared to bone tissues of mice treated with EVs-DiD. Importantly, the modified EVs were well tolerated and showed no evidence of nonspecific side effects or immune response. Besides, our results showed that Ale-EVs could promote the proliferation and differentiation of mouse mesenchymal stem cells in vitro. And it had the antiosteoporotic effects in ovariectomy (OVX)-induced osteoporosis rat model. Conclusions A novel bone-targeting nanoparticle delivery system was developed for osteoporosis therapy. We used the Ale-N3 to modify mMSCs derived EVs by copper-free "click chemistry” to generate a Ale-EVs system. The Ale-EVs had a high affinity for bone and have great potential for clinical applications in osteoporosis therapy with low systemic toxicity.

scholarly journals Oral Bone Tissue Regeneration: Mesenchymal Stem Cells, Secretome, and Biomaterials

2021 ◽  
Vol 22 (10) ◽  
pp. 5236
Author(s):  
Agnese Gugliandolo ◽  
Luigia Fonticoli ◽  
Oriana Trubiani ◽  
Thangavelu S. Rajan ◽  
Guya D. Marconi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Functional Restoration ◽  
Bone Tissue Regeneration ◽  
In Vivo Models

In the last few decades, tissue engineering has become one of the most studied medical fields. Even if bone shows self-remodeling properties, in some cases, due to injuries or anomalies, bone regeneration can be required. In particular, oral bone regeneration is needed in the dentistry field, where the functional restoration of tissues near the tooth represents a limit for many dental implants. In this context, the application of biomaterials and mesenchymal stem cells (MSCs) appears promising for bone regeneration. This review focused on in vivo studies that evaluated bone regeneration using biomaterials with MSCs. Different biocompatible biomaterials were enriched with MSCs from different sources. These constructs showed an enhanced bone regenerative power in in vivo models. However, we discussed also a future perspective in tissue engineering using the MSC secretome, namely the conditioned medium and extracellular vesicles. This new approach has already shown promising results for bone tissue regeneration in experimental models.

scholarly journals Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes

2018 ◽  
Vol 47 (1) ◽  
pp. 11-25 ◽  
Author(s):  
Miguel Tofiño-Vian ◽  
Maria Isabel Guillén ◽  
María Dolores Pérez del Caz ◽  
Antonio Silvestre ◽  
María José Alcaraz
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Conditioned Medium ◽  
Extracellular Vesicles ◽  
Prostaglandin E ◽  
No Production ◽  
Oa Chondrocytes ◽  
Anti Inflammatory

Background/Aims: Chronic inflammation contributes to cartilage degeneration during the progression of osteoarthritis (OA). Adipose tissue-derived mesenchymal stem cells (AD-MSC) show great potential to treat inflammatory and degradative processes in OA and have demonstrated paracrine effects in chondrocytes. In the present work, we have isolated and characterized the extracellular vesicles from human AD-MSC to investigate their role in the chondroprotective actions of these cells. Methods: AD-MSC were isolated by collagenase treatment from adipose tissue from healthy individuals subjected to abdominal lipectomy surgery. Microvesicles and exosomes were obtained from conditioned medium by filtration and differential centrifugation. Chondrocytes from OA patients were used in primary culture and stimulated with 10 ng/ml interleukin(IL)-1β in the presence or absence of AD-MSC microvesicles, exosomes or conditioned medium. Protein expression was investigated by ELISA and immunofluorescence, transcription factor-DNA binding by ELISA, gene expression by real-time PCR, prostaglandin E2 (PGE2) by radioimmunoassay, and matrix metalloproteinase (MMP) activity and nitric oxide (NO) production by fluorometry. Results: In OA chondrocytes stimulated with IL-1β, microvesicles and exosomes reduced the production of inflammatory mediators tumor necrosis factor-α, IL-6, PGE2 and NO. The downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 would lead to the decreased PGE2 production while the effect on NO could depend on the reduction of inducible nitric oxide synthase expression. Treatment of OA chondrocytes with extracellular vesicles also decreased the release of MMP activity and MMP-13 expression whereas the production of the anti-inflammatory cytokine IL-10 and the expression of collagen II were significantly enhanced. The reduction of inflammatory and catabolic mediators could be the consequence of a lower activation of nuclear factor-κB and activator protein-1. The upregulation of annexin A1 specially in MV may contribute to the anti-inflammatory and chondroprotective effects of AD-MSC. Conclusions: Our data support the interest of AD-MSC extracellular vesicles to develop new therapeutic approaches in joint conditions.

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