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Adv Pharm Bull. 2022;12(2): 356-365.
doi: 10.34172/apb.2022.034
  Abstract View: 381
  PDF Download: 181

Research Article

The Combined Thermoresponsive Cell-Imprinted Substrate, Induced Differentiation, and “KLC Sheet” Formation

Neda Keyhanvar 1,2,3* ORCID logo, Nosratollah Zarghami 2, Alexander Seifalian 4, Peyman Keyhanvar 5, Rana Sarvari 6, Roya Salehi 5, Reza Rahbarghazi 1,7, Mohammadreza Ranjkesh 8, Molood Akbarzadeh 3,9, Mahdi Mahdipour 1,10, Mohammad Nouri 1,2,3* ORCID logo

1 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz Iran.
4 Nanotechnology and Regenerative Medicine Centre (Ltd), the London BioScience Innovation Centre, London, UK.
5 Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
7 Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
8 Dermatology & Dermopharmacy Research Team and Department of Dermatology, Sina Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
9 Department of Cellular and Molecular Biology, Faculty of Biological Science, Azarbaijan Shahid Madani University, Tabriz, Iran.
10 Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Author: Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz Iran., Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz Iran. Email keyhanvarn@ tbzmed.ac.ir, nourimd@tbzmed.ac.ir
*Corresponding Author: Mohammad Nouri , Tel: +98 41 33691432, Email: nourimd@tbzmed.ac.ir

Abstract

Purpose: Stem cells can exhibit restorative effects with the commitment to functional cells.Cell-imprinted topographies provide adaptable templates and certain dimensions for thedifferentiation and bioactivity of stem cells. Cell sheet technology using the thermo-responsivepolymers detaches the “cell sheets” easier with less destructive effects on the extracellularmatrix (ECM). Here, we aim to dictate keratinocyte-like differentiation of mesenchymal stemcells (MSCs) by using combined cell imprinting and sheet technology.Methods: We developed the poly dimethyl siloxane (PDMS) substrate having keratinocytecell-imprinted topography grafted with the PNIPAAm polymer. Adipose tissue-derived MSCs(AT-MSCs) were cultured on PDMS substrate for 14 days and keratinocyte-like differentiationmonitored via the expression of involucrin, P63, and cytokeratin 14.Results: Data showed the efficiency of the current protocol in the fabrication of PDMSmolds. The culture of AT-MSCs induced typical keratinocyte morphology and up-regulatedthe expression of cytokeratin-14, Involucrin, and P63 compared to AT-MSCs cultured on theplastic surface (P<0.05). Besides, KLC sheets were generated once slight changes occur in theenvironment temperature.Conclusion: These data showed the hypothesis that keratinocyte cell imprinted substrate canorient AT-MSCs toward KLCs by providing a specific niche and topography.
Keywords: Adipose tissue-derived mesenchymal stem cells, Cell-imprinting, Cell sheet engineering, Differentiation, Poly N-Isopropyl acrylamide (PNIPAAm), Topography

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Submitted: 12 Jul 2020
Revision: 18 Feb 2021
Accepted: 01 May 2021
ePublished: 02 May 2021
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