Title: Differential effects of the extracellular microenvironment on human embryonic stem cells differentiation into keratinocytes and their subsequent replicative lifespan
Authors : Movahednia, Mohammad Mehdi
Kidwai, Fahad Karim
Zou, Yu
Tong, Huei Jinn
Liu, Xiaochen
Islam, Intekhab
Toh, Wei Seong
Raghunath, Michael
Cao, Tong
Published in : Tissue engineering. Part A
Volume(Issue) : 21
Issue : 7-8
Publisher / Ed. Institution : Mary Ann Liebert
Issue Date: 2015
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subject (DDC) : 571: Physiology and related subjects
616: Internal medicine and diseases
Abstract: Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-KertACC) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-KertAFF were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-KertAFF showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell–cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during differentiation of hESCs on subsequent replicative life span and cellular senescence of the differentiated keratinocytes, with implications for use of these cells for applications in tissue engineering and regenerative medicine.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific Journal
DOI : 10.1089/ten.TEA.2014.0551
ISSN: 1937-335X
URI: https://digitalcollection.zhaw.ch/handle/11475/12198
Appears in Collections:Publikationen Life Sciences und Facility Management

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