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Activation of the Bmp2/Smad4 Signaling Pathway for Enhancing Articular Cartilage Regeneration of Mesenchymal Stem Cells Utilizing Chitosan/Alginate Nanoparticles on 3D Extracellular Matrix Scaffold Publisher Pubmed



Zohri M1 ; Arefian E2, 3 ; Azizi Z4 ; Akbari Javar H5 ; Shadboorestan A6 ; Fatahi Y1, 7 ; Chogan F8 ; Taheri M9 ; Karoobi S10 ; Aghaeebakhtiari SH11, 12 ; Bonakdar S13 ; Gazori T14 ; Mohammadi S10 ; Saadatpour F2 Show All Authors
Authors
  1. Zohri M1
  2. Arefian E2, 3
  3. Azizi Z4
  4. Akbari Javar H5
  5. Shadboorestan A6
  6. Fatahi Y1, 7
  7. Chogan F8
  8. Taheri M9
  9. Karoobi S10
  10. Aghaeebakhtiari SH11, 12
  11. Bonakdar S13
  12. Gazori T14
  13. Mohammadi S10
  14. Saadatpour F2
  15. Ghahremani MH1, 10
Show Affiliations
Authors Affiliations
  1. 1. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
  2. 2. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
  3. 3. Pediatric Cell and Gene Therapy Research Center, Tehran University of Medical Sciences
  4. 4. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Departments of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
  6. 6. Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  7. 7. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Institute of Medical Science, University of Toronto, Toronto, Canada
  9. 9. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  10. 10. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
  11. 11. Bioinformatics Research Center, Mashhad University of Medical Science, Mashhad, Iran
  12. 12. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
  13. 13. National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran
  14. 14. Trita Nanomedicine Research Center (TNRC), Trita Third Millennium Pharmaceuticals, Tehran, 1917733831, Iran

Source: International Journal of Biological Macromolecules Published:2024


Abstract

This study investigated the efficacy of using chitosan/alginate nanoparticles loaded with recombinant human bone morphogenetic-2 (rhBMP-2) and SMAD4 encoding plasmid to enhance the chondrogenesis of human bone marrow mesenchymal stem cells (hBM-MSCs) seeded on an extracellular matrix (ECM). The research treatments included the stem cells treated with the biological cocktail (BC), negative control (NC), hBM-MSCs with chondrogenic medium (MCM), hBM-MSCs with naked rhBMP-2 and chondrogenic medium (NB/C), and hBM-MSCs with naked rhBMP-2 and chondrogenic medium plus SMAD4 encoding plasmid transfected with polyethyleneimine (PEI) (NB/C/S/P). The cartilage differentiation was performed with real-time quantitative PCR analysis and alizarin blue staining. The data indicated that the biological cocktail (BC) exhibited significantly higher expression of cartilage-related genes compared to significant differences with MCM and negative control (NC) on chondrogenesis. In the (NB/C/S/P), the expression levels of SOX9 and COLX were lower than those in the BC group. The expression pattern of the ACAN gene was similar to COL2A1 changes suggesting that it holds promising potential for cartilage regeneration. © 2024 Elsevier B.V.
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