Monodispersed β‐Glycerophosphate‐Decorated Bioactive Glass Nanoparticles Reinforce Osteogenic Differentiation of Adipose Stem Cells and Bone Regeneration In Vivo

Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.

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Apoptosis Repressor with Caspase Domain (ARC) Promotes Bone Regeneration of Bone Marrow Derived Mesenchymal Stem Cells via Activating Fgf-2/PI3K/Akt Signaling

10.21203/rs.3.rs-81021/v1 ◽

2020 ◽

Author(s):

Longwei Hu ◽

Yang Wang ◽

Hongya Pan ◽

Kathreena Kadir ◽

Jin Wen ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Cell Apoptosis ◽

Pcr Analysis ◽

New Bone Formation

Abstract Objectives:This study aims to investigate whether ARC could promote survival and enhance osteogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs).Material and methods:Lentivirus transfection method was used to establish ARC overexpressed BMSCs. CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluoresence staining, ALP, ARS assay and RT-PCR analysis. Cells were seeded into CPC scaffolds, then inserted into subcutaneous of nude mice and the defect area of rat’s calvarium. Histological analysis was conducted to evaluate in vivo cell apoptosis and new bone formation ability of ARC overexpressed BMSCs. RNA-seq method was used to detect the possible mechanism of the effect of ARC on BMSCs. Results:ARC can promote BMSCs proliferation and inhibit its cell apoptosis. ARC can enhance BMSCs osteogenic differentiation in vitro. In vivo study revealed ARC can inhibit BMSCs’ apoptosis and increase its new bone formation ability. ARC regulates BMSCs mainly by activating Fgf-2/PI3K/Akt pathway.Conclusions: The present study suggested that ARC is a powerful agent to promote bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

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Dentin-derived Inorganic Minerals Promote the Osteogenesis of Bone Marrow-derived Mesenchymal Stem Cells: Potential Applications for Bone Regeneration

10.21203/rs.3.rs-34650/v1 ◽

2020 ◽

Author(s):

Gang Lei ◽

Yanqiu Wang ◽

Yan Yu ◽

Zehan Li ◽

Jiamin Lu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Mapk Signaling ◽

Control Group ◽

Alizarin Red

Abstract Background Oral and maxillofacial bone loss is highly prevalent among populations and nowadays increased attention has been focused on dentin derivatives as desirable graft materials for bone regeneration. In this study, dentin-derived inorganic minerals (DIM) were fabricated with a high-temperature calcination technique and the effects of DIM on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) and the bone formation were elucidated.Methods The effects of DIM on BMMSCs proliferation, apoptosis capacity were evaluated by CCK-8, flow cytometry and EdU assays. Alkaline phosphatase (ALP) activity detection, ALP staining, alizarin red staining and osteogenic markers expression analysis were performed to investigate the influence of DIM on the osteogenic differentiation of BMMSCs, as well as the relevant signal mechanisms. The model of critical-sized defects in calvarium of rats was constructed for exploring the in vivo efficiency of DIM on bone regeneration.Results Cell viability assays indicated that DIM had no cytotoxicity. BMMSCs cultured with DIM presented a higher level of osteogenic differentiation ability than those in the control group. The activation in ERK and p38 signals was detected in DIM-treated BMMSCs, and both pathways and osteogenic process were suppressed while using ERK inhibitor U0126 and p38 inhibitor SB203580, respectively. Furthermore, the animal experiments revealed that DIM could dramatically enhance new bone formation compared to the control group.Conclusion All these results demonstrated that DIM could promote BMMSCs osteogenic differentiation via triggering ERK and p38 MAPK signaling pathways and be a novel predictable material for facilitating bone formation.

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Bioactive glass induced osteogenic differentiation of human adipose stem cells is dependent on cell attachment mechanism and mitogen-activated protein kinases

10.22203/ecm.v035a05 ◽

2018 ◽

Vol 35 ◽

pp. 54-72 ◽

Cited By ~ 16

Author(s):

M Ojansivu ◽

◽

X Wang ◽

L Hyväri ◽

M Kellomäki ◽

...

Keyword(s):

Stem Cells ◽

Bioactive Glass ◽

Osteogenic Differentiation ◽

Protein Kinases ◽

Cell Attachment ◽

Adipose Stem Cells ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein ◽

Attachment Mechanism ◽

Human Adipose Stem Cells

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Apoptosis Repressor with Caspase Recruitment Domain (ARC) Promotes Bone Regeneration of Bone Marrow-Derived Mesenchymal Stem Cells by Activating Fgf-2/PI3K/Akt Signaling

10.21203/rs.3.rs-81021/v3 ◽

2021 ◽

Author(s):

Longwei Hu ◽

Yang Wang ◽

Hongya Pan ◽

Kathreena Kadir ◽

Jin Wen ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Cell Apoptosis ◽

New Bone Formation ◽

Caspase Recruitment Domain

Abstract Objectives: This study aims to investigate whether Apoptosis repressor with caspase recruitment domain (ARC) could promote survival and enhance osteogenic differentiation of bone marrow -derived mesenchymal stem cells (BMSCs). Materials and methods: The lentivirus transfection method was used to establish ARC -overexpressing BMSCs. The CCK-8 method was used to detect cell proliferation. The BD Pharmingen™ APC Annexin V Apoptosis Detection kit was used to detect cell apoptosis. The osteogenic capacity was investigated by OCN immunofluorescence staining, ALP analysis, ARS assays and RT-PCR analysis. Cells were seeded into calcium phosphate cement (CPC) scaffolds and then inserted subcutaneously into nude mice and the defect area of the rat calvarium. Histological analysis was conducted to evaluate the in vivo cell apoptosis and new bone formation of the ARC -overexpressing BMSCs. RNA-seq was used to detect the possible mechanism of the effect of ARC on BMSCs. Results: ARC promoted BMSC proliferation and inhibited cell apoptosis. ARC enhanced BMSC osteogenic differentiation in vitro. An in vivo study revealed that ARC can inhibit BMSC apoptosis and increase new bone formation. ARC regulates BMSCs mainly by activating the Fgf-2/PI3K/Akt pathway. Conclusions: The present study suggests that A RC is a powerful agent for promoting bone regeneration of BMSCs and provides a promising method for bone tissue engineering.

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MicroRNA-5106-based nanodelivery to enhance osteogenic differentiation and bone regeneration of bone mesenchymal stem cells through targeting of Gsk-3α

Materials Chemistry Frontiers ◽

10.1039/d1qm00367d ◽

2021 ◽

Author(s):

Meng Yu ◽

Bo Lei

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Intracellular Delivery ◽

Bone Mesenchymal Stem Cells ◽

Regeneration Of Bone

This work reports the intracellular delivery of miRNA-5106 into stem cells. The intracellular delivery could efficiently enhance the osteogenic differentiation and in vivo bone regeneration through the targeting the Gsk-3α signaling pathway.

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