eCM (Eur Cell Mater / e Cells & Materials) Not-for-Profit Open Access
Created by Scientists, for Scientists
 ISSN:1473-2262         NLM:100973416 (link)         DOI:10.22203/eCM

2019   Volume No 37 – pages 233-249

Title: Effective use of mesenchymal stem cells in human skin substitutes generated by tissue engineering

Authors: MA Martin-Piedra, CA Alfonso-Rodriguez, A Zapater, D Durand-Herrera, J Chato-Astrain, F Campos, MC Sanchez-Quevedo, M Alaminos, I Garzon

Address: Department of Histology, School of Medicine, University of Granada, Avda/Investigación s/n 18071, Granada, Spain.

E-mail: malaminos at

Abstract: Mesenchymal stem cells (MSCs) can differentiate toward epithelial cells and may be used as an alternative source for generation of heterotypical artificial human skin substitutes, thus, enhancing their development and translation potential to the clinic. The present study aimed at comparing four types of heterotypical human bioengineered skin generated using MSCs as an alternative epithelial cell source. Adipose-tissue-derived stem cells (ADSCs), dental pulp stem cells (DPSCs), Wharton’s jelly stem cells (WJSCs) and bone marrow stem cells (BMSCs) were used for epidermal regeneration on top of dermal skin substitutes. Heterotypic human skin substitutes were evaluated before and after implantation in immune-deficient athymic mice for 30 d. Histological and genetic studies were performed to evaluate extracellular matrix synthesis, epidermal differentiation and human leukocyte antigen (HLA) molecule expression. The four cell types differentiated into keratinocytes, as shown by the expression of cytokeratin 10 and filaggrin 30 d post-grafting; also, they induced dermal fibroblasts responsible for the synthesis of extracellular fibrillar and non-fibrillar components, in a similar way among each other. WJSCs and BMSCs showed higher expression of cytokeratin 10 and filaggrin, suggesting these cells were more prone to epidermal regeneration. The absence of HLA molecules, even when the epithelial layer was differentiated, supports the future clinical use of these substitutes – especially ADSCs, DPSCs and WJSCs – with low rejection risk. MSCs allowed the generation of bioengineered human skin substitutes with potential clinical usefulness. According to their epidermal differentiation potential and lack of HLA antigens, WJSCs should preferentially be used.

Key Words: Mesenchymal stem cells, bioartificial skin, tissue engineering, regenerative medicine.

Publication date: March 29th 2019

Article download: Pages 233-249 (PDF file)

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