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Nanotechnological Applications Hold a Pivotal Position in Boosting Stem Cells Osteogenic Activity: In Vitro and In Vivo Studies

Abstract

This approach was constructed to appraise the therapeutic effectiveness of a single i.v. dose of osteoblasts generated from co-culturing BM-MSCs with nano-HA, Pt-NPs, or Pt-HA-nanocomposite in osteoporotic rats. MSCs were grown, propagated in culture, and characterized. The effect of the suggested nanoplatforms on the survival, osteogenic differentiation, and mineralization of BM-MSCs was assessed by MTT assay, real-time PCR analysis, and Alizarin red S staining, respectively. Thereafter, the generated osteoblasts were employed for the treatment of ovariectomized rats. Our results revealed that the selected nanoplatforms upregulate the expression of osteogenic differentiation related genes (Runx-2 and BMP-2) significantly and enhance calcium deposition in BM-MSCs after 7 and 21 days, respectively, whereas the in vivo study validated that the infusion of the generated osteoblasts considerably downturn serum BALP, BSP, and SOST levels; upswing OSX level; and regain femur bone mineralization and histoarchitecture. Conclusively, the outcomes of this work provide scientific evidence that transplanting osteoblasts derived from differentiation of BM-MSCs in the presence of nanoplatforms in ovariectomized rats restores bone remodeling balance which constitutes a new hope for the treatment of osteoporosis.

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Abbreviations

BALP:

Bone alkaline phosphatase

BM-MSCs:

Bone marrow derived mesenchymal stem cells

BMP-2:

Bone morphogenetic protein 2

BSP:

Bone sialoprotein

Nano-HA:

Nanohydroxyapatite

OSX:

Osterix

Pt-NPs:

Platinum nanoparticles

Pt-HA-nanocomposite:

Platinum-hydroxyapatite-nanocomposite

Runx-2:

Runt-related transcription factor 2

SOST:

Sclerostin

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Acknowledgments

The authors gratefully acknowledge the financial support of the National Research Centre, Egypt (Grant no. P100528) and the technical support of the Science and Technology Development Fund (STDF), Egypt, through Capacity Building program (Grant no. 4880). Also, the authors express sincere appreciation to Prof. Adel Bakeer kholoussy, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University for his kind cooperation in conducting histological examination in this study.

Funding

This work was financially supported by the National Research Centre, Egypt (grant no. P100528).

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Correspondence to Hadeer A. Aglan.

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This study was conducted in strict accordance with the recommendations of the guidelines for the care and use of laboratory animals of the National Research Centre, Egypt. The experimental procedures were endorsed by the Ethical Committee of Medical Research of National Research Centre, Giza, Egypt (Admittance code 15 - 154).

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The authors declare that they have no conflict of interest.

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Aglan, H.A., Ahmed, H.H., Mahmoud, N.S. et al. Nanotechnological Applications Hold a Pivotal Position in Boosting Stem Cells Osteogenic Activity: In Vitro and In Vivo Studies. Appl Biochem Biotechnol 190, 551–573 (2020). https://doi.org/10.1007/s12010-019-03105-y

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Keywords

  • Osteoporosis
  • Bone marrow mesenchymal stem cell
  • Nanoplatforms
  • Osteoblast
  • In vitro
  • In vivo