Sustained release of TGF-β1 via genetically-modified cells induces the chondrogenic differentiation of mesenchymal stem cells encapsulated in alginate sulfate hydrogels

  • Mohammad Askari
  • Shahin Bonakdar
  • Mahdi Habibi Anbouhi
  • Hosein Shahsavarani
  • Saeid Kargozar
  • Vahid KhalajEmail author
  • Mohammad Ali ShokrgozarEmail author
Delivery Systems Original Research
Part of the following topical collections:
  1. Delivery Systems


Strategies based on growth factor (GF) delivery have attracted considerable attention in tissue engineering applications. Among different GFs, transforming growth factor beta 1 (TGF-β1) is considered to be a potent factor for inducing chondrogenesis. In the present study, an expression cassette encoding the TGF-β1 protein was prepared and transfected into the SP2/0-Ag14 cell line. The confocal microscopy of the transfected cells was performed to confirm the correct transfection process. The expression and in vitro release kinetics of the recombinant TGF-β1 were assessed by western blot analysis and ELISA, respectively. Moreover, the biological activity of the expressed protein was compared with that of a commercially available product. The chondrogenic effects of the sustained release of the recombinant TGF-β1 in an in vitro co-culture system were evaluated using a migration assay and real-time PCR. Results of confocal microscopy confirmed the successful transfection of the vector-encoding TGF-β1 protein into the SP2/0-Ag14 cells. The bioactivity of the produced protein was in the range of the commercial product. The sustained release of the TGF-β1 protein via SP2/0-Ag14 cells encapsulated in hydrogels encouraged the migration of adipose-derived MSCs. In addition, the expression analysis of chondrogenesis-related genes revealed that the pretreatment of encapsulated Ad-MSCs cells in alginate sulfate hydrogels through their exposure to the sustained release of TGF-β1 is an efficient approach before transplantation of cells into the body.



This research was generously funded by grants from the National Science Foundation (INSF) through Research Grant No. 92026749 and the Pasteur Institute of Iran.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mohammad Askari
    • 1
  • Shahin Bonakdar
    • 1
  • Mahdi Habibi Anbouhi
    • 1
  • Hosein Shahsavarani
    • 2
    • 3
  • Saeid Kargozar
    • 4
  • Vahid Khalaj
    • 5
    Email author
  • Mohammad Ali Shokrgozar
    • 1
    Email author
  1. 1.National Cell Bank DepartmentPasteur Institute of IranTehranIran
  2. 2.Laboratory of Regenerative Medicine and Biomedical InnovationsPasteur Institute of IranTehranIran
  3. 3.Faculty of Life Sciences and BiotechnologyShahid Beheshti UniversityTehranIran
  4. 4.Department of Modern Sciences and Technologies, School of MedicineMashhad University of Medical SciencesMashhadIran
  5. 5.Medical Biotechnology Department, Biotechnology Research CenterPasteur Institute of IranTehranIran

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