scholarly journals Nanostructured Modifications of Titanium Surfaces Improve Vascular Regenerative Properties of Exosomes Derived from Mesenchymal Stem Cells: Preliminary In Vitro Results

Nanomaterials ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3452
Author(s):  
Chiara Gardin ◽  
Letizia Ferroni ◽  
Yaşar Kemal Erdoğan ◽  
Federica Zanotti ◽  
Francesco De Francesco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Cell Activity ◽  
Electrochemical Anodization ◽  
Material Surface ◽  
Human Mscs ◽  
Related Factors ◽  
Common Procedure

(1) Background: Implantation of metal-based scaffolds is a common procedure for treating several diseases. However, the success of the long-term application is limited by an insufficient endothelialization of the material surface. Nanostructured modifications of metal scaffolds represent a promising approach to faster biomaterial osteointegration through increasing of endothelial commitment of the mesenchymal stem cells (MSC). (2) Methods: Three different nanotubular Ti surfaces (TNs manufactured by electrochemical anodization with diameters of 25, 80, or 140 nm) were seeded with human MSCs (hMSCs) and their exosomes were isolated and tested with human umbilical vein endothelial cells (HUVECs) to assess whether TNs can influence the secretory functions of hMSCs and whether these in turn affect endothelial and osteogenic cell activities in vitro. (3) Results: The hMSCs adhered on all TNs and significantly expressed angiogenic-related factors after 7 days of culture when compared to untreated Ti substrates. Nanomodifications of Ti surfaces significantly improved the release of hMSCs exosomes, having dimensions below 100 nm and expressing CD63 and CD81 surface markers. These hMSC-derived exosomes were efficiently internalized by HUVECs, promoting their migration and differentiation. In addition, they selectively released a panel of miRNAs directly or indirectly related to angiogenesis. (4) Conclusions: Preconditioning of hMSCs on TNs induced elevated exosomes secretion that stimulated in vitro endothelial and cell activity, which might improve in vivo angiogenesis, supporting faster scaffold integration.

scholarly journals Environmental Benzopyrene Attenuates Stemness of Placenta-Derived Mesenchymal Stem Cells via Aryl Hydrocarbon Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
June Seok Heo ◽  
Ja-Yun Lim ◽  
Sangshin Pyo ◽  
Dae Wui Yoon ◽  
Dongsook Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Cell Activity ◽  
Bone Diseases ◽  
Purine Derivative ◽  
Aryl Hydrocarbon ◽  
Polycyclic Aromatic

The toxic effects of particulate matter have been linked to polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene. PAHs are potent inducers of the aryl hydrocarbon receptor (AhR), which is an expressed nuclear receptor that senses environmental stimuli and modulates gene expression. Even though several studies have shown that the benzopyrene (BP) of chemical pollutants significantly impaired stem cell activity, the exact molecular mechanisms were not clearly elucidated. In the present study, we aimed to investigate the effects of BP on placenta-derived mesenchymal stem cells (PD-MSCs) in vitro. We found that the AhR in PD-MSCs was expressed under the treatment of BP, and its activation markedly disrupted osteogenic differentiation through the alteration of stemness activity of PD-MSCs. Moreover, BP treatment significantly reduced the proliferation activity of PD-MSCs and expression of pluripotent markers through the induction of AhR. Treatment with StemRegenin 1 (SR1), a purine derivative that antagonizes the AhR, effectively prevented BP-induced reduction of the proliferation and differentiation activity of PD-MSCs. In this study, we found that BP treatment in PD-MSCs markedly obstructs PD-MSC stemness through AhR signaling. Noteworthy, SR1-mediated MSC application will contribute to new perspectives on MSC-based therapies for air pollution-related bone diseases.

In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells

2006 ◽  
Vol 340 (2) ◽  
pp. 639-647 ◽  
Author(s):  
Mehdi Kadivar ◽  
Shohreh Khatami ◽  
Yousef Mortazavi ◽  
Mohammad Ali Shokrgozar ◽  
Mohammad Taghikhani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Human Umbilical Vein

Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 4120-4126 ◽  
Author(s):  
Xiao-Xia Jiang ◽  
Yi Zhang ◽  
Bing Liu ◽  
Shuang-Xi Zhang ◽  
Ying Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Human Mesenchymal Stem Cells ◽  
Interleukin 4 ◽  
Human Mscs ◽  
Gm Csf ◽  
Macrophage Colony ◽  
And Function

AbstractMesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.

scholarly journals Mesenchymal stem cells are injured by complement after their contact with serum

Blood ◽  
2012 ◽  
Vol 120 (17) ◽  
pp. 3436-3443 ◽  
Author(s):  
Yan Li ◽  
Feng Lin
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Surface ◽  
Complement Activation ◽  
Human Mscs ◽  
Cellular Injury ◽  
Allogeneic Mscs ◽  
Complement Regulators

Abstract Despite the potent immunosuppressive activity that mesenchymal stem cells (MSCs) display in vitro, recent clinical trial results are disappointing, suggesting that MSC viability and/or function are greatly reduced after infusion. In this report, we demonstrated that human MSCs activated complement of the innate immunity after their contact with serum. Although all 3 known intrinsic cell-surface complement regulators were present on MSCs, activated complement overwhelmed the protection of these regulators and resulted in MSCs cytotoxicity and dysfunction. In addition, autologous MSCs suffered less cellular injury than allogeneic MSCs after contacting serum. All 3 complement activation pathways were involved in generating the membrane attack complex to directly injure MSCs. Supplementing an exogenous complement inhibitor, or up-regulating MSC expression levels of CD55, one of the cell-surface complement regulators, helped to reduce the serum-induced MSC cytotoxicity. Finally, adoptively transferred MSCs in complement deficient mice or complement-depleted mice showed reduced cellular injury in vivo compared with those in wild type mice. These results indicate that complement is integrally involved in recognizing and injuring MSCs after their infusion, suggesting that autologous MSCs may have ad-vantages over allogeneic MSCs, and that inhibiting complement activation could be a novel strategy to improve existing MSC-based therapies.

Distribution of Seeded Mesenchymal Stem Cells on Hydroxyapatite Porous Ceramics

2007 ◽  
Vol 330-332 ◽  
pp. 1141-1144 ◽  
Author(s):  
Mika Tadokoro ◽  
Noriko Kotobuki ◽  
Akira Oshima ◽  
Hajime Ohgushi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
In Vitro Culture ◽  
Porous Ceramic ◽  
Porous Ceramics ◽  
Human Mscs ◽  
Ceramic Scaffold ◽  
Before And After

This study focused on in vivo osteogenic capability of bone marrow mesenchymal stem cells (MSCs) seeded on ceramic scaffold. Human MSCs from a single donor were seeded on hydroxyapatite porous ceramic (HAP) and were induced to the osteogenic lineage during in vitro culture condition, then the MSCs/HAP composites were implanted subcutaneously into immunodeficient rats. The cellular activities of the composites were assayed in order to evaluate the distribution and differentiation capability of seeded MSCs before and after implantation. These results showed that the new bone, after implantation, was derived from the donor MSCs, which adhered to the surface of the ceramics pore areas during in vitro culture. Therefore, the engrafted donor cells proliferated and showed continuous osteogenic differentiation within the recipients. Consequently, our study demonstrates the usefulness of MSCs/HAP composites for clinical applications.

scholarly journals Rheb1-Deficient Neutrophils Promote Hematopoietic Stem/Progenitor Cell Proliferation via Mesenchymal Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Juan Gao ◽  
Shuaibing Hou ◽  
Shengnan Yuan ◽  
Yuxia Wang ◽  
Yanan Gao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myeloid Cells ◽  
Human Mscs ◽  
Hematopoietic Stem ◽  
Progenitor Cell Proliferation ◽  
High Level ◽  
Lower Expression

Myeloid cells have been identified as hematopoietic stem cell (HSC)-regulating cells. However, the mechanisms by which myeloid cells regulate the function of HSCs are not fully defined. Our previous study indicated that the HSCs are over-expanded in Vav1-Cre;Rheb1fl/fl mice. Here, using in vivo and in vitro models, we found that Rheb1-deficient neutrophils remodeled the bone marrow environment and induced expansion of HSCs in vivo. Further studies showed that loss of Rheb1 impaired neutrophils’ ability to secrete IL-6, led mesenchymal stem cells (MSCs) to produce more SCF, and promote HSC proliferation. We further found that IL-6 suppressed SCF mRNA expression in human MSCs. Interesting, the high level of IL-6 was also related with poor survival of chronic myeloid leukemia (CML) patients, and higher expression of IL-6 in CML cells is associated with the lower expression of SCF in MSCs in patients. Our studies suggested that blocking IL-6 signaling pathway might stimulate MSCs to secrete more SCF, and to support hematopoietic stem/progenitor cells proliferation.

scholarly journals IFN-γ Enhances the Efficacy of Exosomes Derived from Mesenchymal Stem Cells in Myocardial Infarction Rats via miR-21 Stimulated by STAT1

2021 ◽  
Author(s):  
Jian Zhang ◽  
Yao Lu ◽  
Yangming Mao ◽  
Yue Yu ◽  
Tianyu Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Ifn Γ

Abstract Background: Mesenchymal stem cells (MSCs) activated with IFN-γ elicit more powerful physical effects. Exosomes (Exos) secreted from MSCs have protective against myocardial injury. The aim of this study was to investigate whether Exsos derived from IFN-γ-pretreated MSCs exhibit more potent cardioprotective function and the underlying mechanisms. Methods: Exos were isolated from MSCs (Ctrl-Exo) and IFN-γ-primed MSCs (IFN-γ-Exo) and were then delivered to H9c2 cells or human umbilical vein endothelial cells (HUVECs) in vitro under oxygen and glucose deprivation (OGD) condition or in vivo in an infarcted rat heart. RNA sequencing was to identify the different expressed functional transcription factor (TF). Quantitative reverse transcription-PCR (qPCR) was to confirm the upregulated TF and miRNA in IFN-γ-primed MSCs. Dual-luciferase reporter gene assay were to analyze the transcriptional regulation of miRNAs by STAT1. The target of miR-21-5p (miR-21) was disclosed by luciferase reporter assays and qPCR. The function of BTG2 was verified in vitro under OGD condition.Result: IFN-γ-Exo accelerated migration, tube-like structure formation, and prevented H9c2 from OGD-induced apoptosis. Similarly, IFN-γ-Exo leaded to further reduction in fibrosis size, reduced cardiomyocyte apoptosis and improved cardiac function compared to Ctrl-Exo. miR-21 was significantly upregulated in both IFN-γ-primed MSCs and IFN-γ-Exo. STAT1 transcriptionally induced miR-21 expression. Up-regulated miR-21 can inhibit the expression of BTG2. BTG2 promoted H9c2 cells apoptosis and reversed the protective effect of miR-21 under OGD environment.Conclusion: IFN-γ-Exo have enhanced therapeutic efficacy against acute MI possibly through promoting angiogenesis and anti-apoptotic effect through increasing the level of miR-21, which directly targeted on BTG2.

Microrna-342-3p Loaded by Human Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Attenuates Deep Vein Thrombosis by Downregulating EDNRA

2021 ◽  
Author(s):  
Zhiyu Pan ◽  
Qian Chen ◽  
Hongjian Ding ◽  
Huaqing Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Deep Vein Thrombosis ◽  
Umbilical Cord ◽  
Umbilical Vein ◽  
Dynamic Balance ◽  
Human Umbilical Cord ◽  
Vein Thrombosis ◽  
Deep Vein

Abstract Objectivexosomes (exos) exert biological functions to maintain the dynamic balance of cells and tissues by transferring biological cargo to recipient cells. Thus, this study explored human umbilical cord mesenchymal stem cells (hucMSCs)-derived exo transfer of microRNA (miR)-342-3p in deep vein thrombosis (DVT).MethodsHucMSCs were isolated and transfected with miR-342-3p antagomir/agomir. Then, hucMSCs-exos were extracted and injected into rats with DVT to observe inflammation and pathological damage in thrombotic vein. HucMSCs-exos were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro to observe angiogenesis. miR-342-3p and endothelin A receptor (EDNRA) expression in rats with DVT, as well as their interaction was analyzed.ResultsmiR-342-3p was downregulated and EDNRA was upregulated in rats with DVT. HucMSCs-exos induced the repair of venous thrombosis and suppressed inflammation and pathological injury in rats with DVT, as well as promoted angiogenesis of HUVECs. Upregulated miR-342-3p delivery by hucMSCs-exos alleviated DVT in rats and improved angiogenesis of HUVECs, while downregulated miR-342-3p performed oppositely. miR-342-3p targeted EDNRA, and the effect of hucMSCs-exos transfer of upregulated miR-342-3p was rescued by overexpressing EDNRA.ConclusionBriefly, miR-342-3p loaded by hucMSCs-exos attenuates DVT by downregulating EDNRA, offering a novel direction to treat DVT.

scholarly journals Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation

2013 ◽  
Vol 18 (2) ◽  
Author(s):  
Dana Foudah ◽  
Juliana Redondo ◽  
Cristina Caldara ◽  
Fabrizio Carini ◽  
Giovanni Tredici ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Adipogenic Differentiation ◽  
Neural Cells ◽  
Human Mscs ◽  
Differentiation Markers ◽  
Neuronal Markers ◽  
Wide Range

AbstractMesenchymal stem cells (MSCs) are multipotent cells that are able to differentiate into mesodermal lineages (osteogenic, adipogenic, chondrogenic), but also towards non-mesodermal derivatives (e.g. neural cells). Recent in vitro studies revealed that, in the absence of any kind of differentiation stimuli, undifferentiated MSCs express neural differentiation markers, but the literature data do not all concur. Considering their promising therapeutic potential for neurodegenerative diseases, it is very important to expand our knowledge about this particular biological property of MSCs. In this study, we confirmed the spontaneous expression of neural markers (neuronal, glial and progenitor markers) by undifferentiated human MSCs (hMSCs) and in particular, we demonstrated that the neuronal markers βIII-tubulin and NeuN are expressed by a very high percentage of hMSCs, regardless of the number of culture passages and the culture conditions. Moreover, the neuronal markers βIII-tubulin and NeuN are still expressed by hMSCs after in vitro osteogenic and adipogenic differentiation. On the other hand, chondrogenically differentiated hMSCs are negative for these markers. Our findings suggest that the expression of neuronal markers could be common to a wide range of cellular types and not exclusive for neuronal lineages. Therefore, the expression of neuronal markers alone is not sufficient to demonstrate the differentiation of MSCs towards the neuronal phenotype. Functional properties analysis is also required.

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