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Cell sheet biofabrication by co-administration of mesenchymal stem cells secretome and vitamin C on thermoresponsive polymer

  • Tissue Engineering Constructs and Cell Substrates
  • Original Research
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Abstract

Cell sheet technology aims at replacement of artificial extracellular matrix (ECM) or scaffolds, popular in tissue engineering, with natural cell derived ECM. Adipose tissue mesenchymal stem cells (ASCs) have the ability of ECM secretion and presented promising outcomes in clinical trials. As well, different studies found that secretome of ASCs could be suitable for triggering cell free regeneration induction. The aim of this study was to investigate the effect of using two bio-factors: secretome of ASCs (SE) and vitamin C (VC) for cell sheet engineering on a thermosensitive poly N-isopropyl acryl amide-Methacrylic acid (P(NIPAAm-MAA)) hydrogel. The results revealed that using thermosensitive P(NIPAAm-MAA) copolymer as matrix for cell sheet engineering lead to a rapid ON⁄OFF adhesion/deadhesion system by reducing temperature without enzymatic treatment (complete cell sheet release takes just 6 min). In addition, our study showed the potential of SE for inducing ASCs sheet formation. H&E staining exhibited the properties of a well-formed tissue layer with a dense ECM in sheets prepared by both SE and VC factors, as compared to those of VC or SE alone. Functional synergism of SE and VC exhibited statistically significant enhanced functionality regarding up-regulation of stemness genes expression, reduced β-galactosidase associated senescence, and facilitated sheet release. Additionally, alkaline phosphatase activity (ALP), mineralized deposits and osteoblast matrix around cells confirmed a better performance of ostogenic differentiation of ASCs induced by VC and SE. It was concluded that SE of ASCs and VC could be outstanding biofactors applicable for cell sheet technology.

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Acknowledgements

This project was supported financially by Umbilical Cord Stem Cell Research Center, Tabriz University of Medical Science (Grant number: 5/104/1149).

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Authors and Affiliations

  1. The Umbilical Cord Stem Cell Research Center (UCSRC), Tabriz University of Medical Sciences, Tabriz, Iran

    Behnaz Banimohammad Shotorbani, Nosratollah Zarghami & Effat Alizadeh

  2. Research Institute for Fundamental Sciences (RIFS), University of Tabriz, Tabriz, Iran

    Behnaz Banimohammad Shotorbani & Abolfazl Barzegar

  3. Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden

    Helder André

  4. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Nosratollah Zarghami & Effat Alizadeh

  5. Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Roya Salehi

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  1. Behnaz Banimohammad Shotorbani
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  2. Helder André
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  3. Abolfazl Barzegar
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  4. Nosratollah Zarghami
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  5. Roya Salehi
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Correspondence to Roya Salehi or Effat Alizadeh.

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Shotorbani, B.B., André, H., Barzegar, A. et al. Cell sheet biofabrication by co-administration of mesenchymal stem cells secretome and vitamin C on thermoresponsive polymer. J Mater Sci: Mater Med 29, 170 (2018). https://doi.org/10.1007/s10856-018-6180-z

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