scholarly journals Bioactive and Topographically-Modified Electrospun Membranes for the Creation of New Bone Regeneration Models

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1341
Author(s):  
Dina Abdelmoneim ◽  
Ghsaq M. Alhamdani ◽  
Thomas E. Paterson ◽  
Martin E. Santocildes Romero ◽  
Beatriz J. C. Monteiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Bone Regeneration ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bone Tissue Regeneration ◽  
Ageing Population ◽  
Native Bone ◽  
The Creation

Bone injuries that arise from trauma, cancer treatment, or infection are a major and growing global challenge. An increasingly ageing population plays a key role in this, since a growing number of fractures are due to diseases such as osteoporosis, which place a burden on healthcare systems. Current reparative strategies do not sufficiently consider cell-substrate interactions that are found in healthy tissues; therefore, the need for more complex models is clear. The creation of in vitro defined 3D microenvironments is an emerging topographically-orientated approach that provides opportunities to apply knowledge of cell migration and differentiation mechanisms to the creation of new cell substrates. Moreover, introducing biofunctional agents within in vitro models for bone regeneration has allowed, to a certain degree, the control of cell fate towards osteogenic pathways. In this research, we applied three methods for functionalizing spatially-confined electrospun artificial microenvironments that presented relevant components of the native bone stem cell niche. The biological and osteogenic behaviors of mesenchymal stromal cells (MSCs) were investigated on electrospun micro-fabricated scaffolds functionalized with extracellular matrix (ECM) proteins (collagen I), glycosaminoglycans (heparin), and ceramic-based materials (bioglass). Collagen, heparin, and bioglass (BG) were successfully included in the models without modifying the fibrous structures offered by the polycaprolactone (PCL) scaffolds. Mesenchymal stromal cells (MSCs) were successfully seeded in all the biofunctional scaffolds and they showed an increase in alkaline phosphatase production when exposed to PCL/BG composites. This research demonstrates the feasibility of manufacturing smart and hierarchical artificial microenvironments for studying stem cell behavior and ultimately the potential of incorporating these artificial microenvironments into multifunctional membranes for bone tissue regeneration

scholarly journals The Role of Prep1 in the Regulation of Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3639 ◽  
Author(s):  
Giorgia Maroni ◽  
Daniele Panetta ◽  
Raffaele Luongo ◽  
Indira Krishnan ◽  
Federica La Rosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Gene Dosage ◽  
Homeobox Gene ◽  
Fate Decision

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.

scholarly journals Chelidonic Acid and Its Derivatives from Saussurea Controversa: Isolation, Structural Elucidation and Influence on the Osteogenic Differentiation of Multipotent Mesenchymal Stromal Cells In Vitro

Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 189 ◽  
Author(s):  
Elena Avdeeva ◽  
Elvira Shults ◽  
Tatyana Rybalova ◽  
Yaroslav Reshetov ◽  
Ekaterina Porokhova ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Mass ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Bone Tissue Regeneration ◽  
X Ray ◽  
Icp Ms ◽  
First Time ◽  
Asteraceae Family

4-oxo-4H-pyran-2.6-dicarboxylic acid (chelidonic acid, ChA) in the native state and in the complex with calcium [Ca(ChA)(H2O)3], named saucalchelin (CaChA), was isolated from the extract of Saussurea controversa leaves for the first time for the Asteraceae family. The structure of ChA was determined by NMR, MS and confirmed by X-ray analysis of its monomethyl ester, and CaChA was described by IR, ICP-MS, CHN analysis. The yield of ChA and CaChA was 45 mg/g and 70 mg/g of extract, respectively. The osteogenic activity of ChA, n-monobutyl ester of chelidonic acid, and CaChA has been studied in vitro in a 21-day culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in a standard nutrient medium without osteogenic supplements. CaChA significantly stimulated the growth of cell mass and differentiation of hAMMSCs into osteoblasts with subsequent mineralization of the culture and it may be a promising substance for accelerating bone tissue regeneration and engineering.

scholarly journals Mapping the structure and biological functions within mesenchymal bodies using microfluidics

2020 ◽  
Vol 6 (10) ◽  
pp. eaaw7853 ◽  
Author(s):  
Sébastien Sart ◽  
Raphaël F.-X. Tomasi ◽  
Antoine Barizien ◽  
Gabriel Amselem ◽  
Ana Cumano ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Actin Polymerization ◽  
Bone Repair ◽  
Spatial Organization ◽  
Molecular Signaling ◽  
Correlative Analysis

Organoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.

scholarly journals Mapping Structure and Biological Functions within Mesenchymal Bodies using Microfluidics

2019 ◽  
Author(s):  
Sébastien Sart ◽  
Raphaël F.-X. Tomasi ◽  
Antoine Barizien ◽  
Gabriel Amselem ◽  
Ana Cumano ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Actin Polymerization ◽  
Bone Repair ◽  
Spatial Organization ◽  
Molecular Signaling ◽  
Correlative Analysis

AbstractOrganoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.

scholarly journals Mesenchymal Stromal Cells Do Not Increase the Risk of Viral Reactivation Nor the Severity of Viral Events in Recipients of Allogeneic Stem Cell Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Giovanna Lucchini ◽  
Erica Dander ◽  
Fabio Pavan ◽  
Irene Di Ceglie ◽  
Adriana Balduzzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Viral Reactivation ◽  
Cytotoxic Lymphocyte ◽  
Post Transplantation ◽  
Historical Cohort

Mesenchymal stromal cells (MSC) are tested in clinical trials to treat graft versus host disease (GvHD) after stem cell transplantation (SCT).In vitrostudies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts) receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

scholarly journals Dexamethasone Induces Changes in Osteogenic Differentiation of Human Mesenchymal Stromal Cells via SOX9 and PPARG, but Not RUNX2

2021 ◽  
Vol 22 (9) ◽  
pp. 4785
Author(s):  
Elena Della Bella ◽  
Antoine Buetti-Dinh ◽  
Ginevra Licandro ◽  
Paras Ahmad ◽  
Valentina Basoli ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Sox9 Expression ◽  
Approximate Bayesian ◽  
Adipogenic Effect ◽  
Gene Expression Levels

Despite the huge body of research on osteogenic differentiation and bone tissue engineering, the translation potential of in vitro results still does not match the effort employed. One reason might be that the protocols used for in vitro research have inherent pitfalls. The synthetic glucocorticoid dexamethasone is commonly used in protocols for trilineage differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). However, in the case of osteogenic commitment, dexamethasone has the main pitfall of inhibiting terminal osteoblast differentiation, and its pro-adipogenic effect is well known. In this work, we aimed to clarify the role of dexamethasone in the osteogenesis of hBMSCs, with a particular focus on off-target differentiation. The results showed that dexamethasone does induce osteogenic differentiation by inhibiting SOX9 expression, but not directly through RUNX2 upregulation as it is commonly thought. Rather, PPARG is concomitantly and strongly upregulated, leading to the formation of adipocyte-like cells within osteogenic cultures. Limiting the exposure to dexamethasone to the first week of differentiation did not affect the mineralization potential. Gene expression levels of RUNX2, SOX9, and PPARG were simulated using approximate Bayesian computation based on a simplified theoretical model, which was able to reproduce the observed experimental trends but with a different range of responses, indicating that other factors should be integrated to fully understand how dexamethasone influences cell fate. In summary, this work provides evidence that current in vitro differentiation protocols based on dexamethasone do not represent a good model, and further research is warranted in this field.

scholarly journals Apoptotic mesenchymal stromal cells support osteoclastogenesis while inhibiting multinucleated giant cells formation in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paul Humbert ◽  
Meadhbh Á. Brennan ◽  
Julien De Lima ◽  
Régis Brion ◽  
Annie Adrait ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Quantitative Proteomics ◽  
Giant Cells ◽  
Multinucleated Giant Cells ◽  
Short Term ◽  
Before And After ◽  
Induced Apoptosis

AbstractIn bone regeneration induced by the combination of mesenchymal stromal cells (MSCs) and calcium-phosphate (CaP) materials, osteoclasts emerge as a pivotal cell linking inflammation and bone formation. Favorable outcomes are observed despite short-term engraftments of implanted MSCs, highlighting their major paracrine function and the possible implication of cell death in modulating their secretions. In this work, we focused on the communication from MSCs towards osteoclasts-like cells in vitro. MSCs seeded on a CaP biomaterial or undergoing induced apoptosis produced a conditioned media favoring the development of osteoclasts from human CD14+ monocytes. On the contrary, MSCs’ apoptotic secretion inhibited the development of inflammatory multinucleated giant cells formed after IL-4 stimulation. Components of MSCs’ secretome before and after apoptotic stress were compared using mass spectrometry-based quantitative proteomics and a complementary immunoassay for major cytokines. CXCR-1 and CXCR-2 ligands, primarily IL-8/CXCL-8 but also the growth-regulated proteins CXCL-1, -2 or -3, were suggested as the major players of MSCs’ pro-osteoclastic effect. These findings support the hypothesis that osteoclasts are key players in bone regeneration and suggest that apoptosis plays an important role in MSCs’ effectiveness.

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