Investigation into the effects of leukemia inhibitory factor on the bone repair capacity of BMSCs-loaded BCP scaffolds in the mouse calvarial bone defect model

Liang, Youde; Zhou, Ruiping; Liu, Xin; Liu, Zhikang; You, Lin; Chen, Chang; Ye, Xiaoling

doi:10.1007/s10863-021-09899-z

Cited by 2 publications

(2 citation statements)

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“…BMSCs begin to die within 3 days of implantation into the ectopic osteogenic site and are barely detectable at 14 days [ 11 ]. Our previous study also found that BMSCs undergo significant apoptosis under hypoxic environment [ 12 ]. Therapeutic applications of BMSCs are limited due to the sensitivity to oxidative stress, leading to apoptosis of transplanted BMSCs in damaged bone areas [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Leukemia Inhibitory Factor Facilitates Self-Renewal and Differentiation and Attenuates Oxidative Stress of BMSCs by Activating PI3K/AKT Signaling

Liang

Zhou

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) remains a hopeful therapeutic approach for bone defect reconstruction. Herein, we investigated the effects and mechanisms of leukemia inhibitory factor (LIF) in the function and viability of hypoxic BMSCs as well as bone defect repair. Methods. The effects of LIF on apoptosis (flow cytometry, TUNEL staining), mitochondrial activity (JC-1 staining), proliferation (colony formation, EdU staining), and differentiation (CD105, CD90, and CD29 via flow sorting) were examined in hypoxic BMSCs. LIF, LIFR, gp130, Keap1, Nrf2, antioxidant enzymes (SOD1, catalase, GPx-3), bone-specific matrix proteins (ALP, BSP, OCN), PI3K, and Akt were detected via immunoblotting or immunofluorescent staining. BMSCs combined with biphasic calcium phosphate scaffolds were implanted into calvarial bone defect mice, and the therapeutic effect of LIF on bone defect was investigated. Results. Hypoxic BMSCs had increased apoptosis and oxidative stress and reduced mitochondrial activity. Additionally, LIF, LIFR, and gp130 were upregulated and PI3K/Akt activity was depressed in hypoxic BMSCs. Upregulated LIF alleviated apoptosis and oxidative stress and heightened mitochondrial activity and PI3K/Akt signaling in hypoxic BMSCs. Additionally, LIF overexpression promoted self-renewal and osteogenic differentiation of BMSCs with hypoxic condition. Mechanically, LIF facilitated self-renewal and differentiation as well as attenuated oxidative stress of BMSCs through enhancing PI3K/AKT signaling activity. Implantation of LIF-overexpressed BMSC-loaded BCP scaffolds promoted osteogenesis as well as alleviated oxidative stress and apoptosis through PI3K/Akt signaling. Conclusion. Our findings demonstrate that LIF facilitates self-renewal and differentiation and attenuates oxidative stress of BMSCs by PI3K/AKT signaling.

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Section: Introductionmentioning

confidence: 99%

Leukemia Inhibitory Factor Facilitates Self-Renewal and Differentiation and Attenuates Oxidative Stress of BMSCs by Activating PI3K/AKT Signaling

Liang

Zhou

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In histological assessment, the criteria were presented in Table 1. Osteoblastic/osteoclastic activity, osteoid tissue formation, development of blood vessels, scaffold degradation, and hard tissue response were evaluated 24 . After the third and eighth weeks of operation, the femur bones were removed for proper sampling and fixed with a 10% formaldehyde solution.…”

Section: Methodsmentioning

confidence: 99%

The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis

et al. 2023

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Alginate (ALG) is a biocompatible and biodegradable polymer. Mechanical weakness is one of the main problems for the alginate-based scaffolds. Various plasticizer additives or modifications tested to improve the mechanical properties. In the presented study, ALG plasticized with triacetin (TA), and tributyl citrate (TBC) than tested on bone healing. In the presented study, the alginate modified with triacetin or tributyl citrate. In-vitro, and in-vivo efficiency of the scaffolds tested on bone tissue regeneration. Scaffolds fabricated by solvent casting, and physicochemical characterizations performed. Monocytes (THP-1) cultured with scaffolds, and macrophage-released cytokines was determined. In-vivo efficacy of the scaffolds was tested in the rat drill hole model. Alginate and tributyl citrate-modified scaffolds have no cytotoxic effect on osteoblastic cells (MC-3T3). Tributyl citrate modification increased tumor necrosis factor-alpha (TNF-alpha) level but did not increase interleukin -1 beta (IL-1 beta) level. In vivo studies showed that osteoblastic growth was significant in alginate and triacetin-modified scaffolds. However, the best values for osteoclastic activity and osteoid tissue formation seen in the triacetin modification. The results demonstrated that the modified alginate scaffolds were more successful than non-modified alginate scaffolds and can used as long-term bone repairing treatments.

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Investigation into the effects of leukemia inhibitory factor on the bone repair capacity of BMSCs-loaded BCP scaffolds in the mouse calvarial bone defect model

Cited by 2 publications

References 40 publications

Leukemia Inhibitory Factor Facilitates Self-Renewal and Differentiation and Attenuates Oxidative Stress of BMSCs by Activating PI3K/AKT Signaling

Leukemia Inhibitory Factor Facilitates Self-Renewal and Differentiation and Attenuates Oxidative Stress of BMSCs by Activating PI3K/AKT Signaling

The effect of alginate scaffolds on bone healing in defects formed with drilling model in rat femur diaphysis

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