Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition

Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significa...

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Main Authors:	Rothdiener, Miriam, Hegemann, Miriam, Uynuk-Ool, Tatiana, Walters, Brandan, Papugy, Piruntha, Nguyen, Phong, Claus, Valentin, Seeger, Tanja, Stoeckle, Ulrich, Boehme, Karen A., Aicher, Wilhelm K., Stegemann, Jan P., Hart, Melanie L., Kurz, Bodo, Klein, Gerd, Rolauffs, Bernd
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075785/

id	pubmed-5075785
recordtype	oai_dc
spelling	pubmed-50757852016-10-28 Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition Rothdiener, Miriam Hegemann, Miriam Uynuk-Ool, Tatiana Walters, Brandan Papugy, Piruntha Nguyen, Phong Claus, Valentin Seeger, Tanja Stoeckle, Ulrich Boehme, Karen A. Aicher, Wilhelm K. Stegemann, Jan P. Hart, Melanie L. Kurz, Bodo Klein, Gerd Rolauffs, Bernd Article Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significantly increased expression of SMC markers, compared to non-stretched controls. First, we generated dense collagen type I sheets by mechanically compressing collagen hydrogels. Atomic force microscopy revealed a nanoscale stiffness range known to support myogenic differentiation. Further characterization revealed viscoelasticity and stable biomechanical properties under cyclic stretch with >99% viable adherent human MSC. MSCs on collagen sheets demonstrated a significantly increased mRNA but not protein expression of SMC markers, compared to on culture flasks. However, cyclic stretch of MSCs on collagen sheets significantly increased both mRNA and protein expression of α-smooth muscle actin, transgelin, and calponin versus plastic and non-stretched sheets. Thus, lineage-specific stiffness and cyclic stretch can be applied together for inducing MSC differentiation towards SMCs without the addition of recombinant growth factors or other soluble factors. This represents a novel stimulation method for modulating the phenotype of MSCs towards SMCs that could easily be incorporated into currently available methodologies to obtain a more targeted control of MSC phenotype. Nature Publishing Group 2016-10-24 /pmc/articles/PMC5075785/ /pubmed/27775041 http://dx.doi.org/10.1038/srep35840 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rothdiener, Miriam Hegemann, Miriam Uynuk-Ool, Tatiana Walters, Brandan Papugy, Piruntha Nguyen, Phong Claus, Valentin Seeger, Tanja Stoeckle, Ulrich Boehme, Karen A. Aicher, Wilhelm K. Stegemann, Jan P. Hart, Melanie L. Kurz, Bodo Klein, Gerd Rolauffs, Bernd
spellingShingle	Rothdiener, Miriam Hegemann, Miriam Uynuk-Ool, Tatiana Walters, Brandan Papugy, Piruntha Nguyen, Phong Claus, Valentin Seeger, Tanja Stoeckle, Ulrich Boehme, Karen A. Aicher, Wilhelm K. Stegemann, Jan P. Hart, Melanie L. Kurz, Bodo Klein, Gerd Rolauffs, Bernd Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition
author_facet	Rothdiener, Miriam Hegemann, Miriam Uynuk-Ool, Tatiana Walters, Brandan Papugy, Piruntha Nguyen, Phong Claus, Valentin Seeger, Tanja Stoeckle, Ulrich Boehme, Karen A. Aicher, Wilhelm K. Stegemann, Jan P. Hart, Melanie L. Kurz, Bodo Klein, Gerd Rolauffs, Bernd
author_sort	Rothdiener, Miriam
title	Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition
title_short	Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition
title_full	Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition
title_fullStr	Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition
title_full_unstemmed	Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition
title_sort	stretching human mesenchymal stromal cells on stiffness-customized collagen type i generates a smooth muscle marker profile without growth factor addition
description	Using matrix elasticity and cyclic stretch have been investigated for inducing mesenchymal stromal cell (MSC) differentiation towards the smooth muscle cell (SMC) lineage but not in combination. We hypothesized that combining lineage-specific stiffness with cyclic stretch would result in a significantly increased expression of SMC markers, compared to non-stretched controls. First, we generated dense collagen type I sheets by mechanically compressing collagen hydrogels. Atomic force microscopy revealed a nanoscale stiffness range known to support myogenic differentiation. Further characterization revealed viscoelasticity and stable biomechanical properties under cyclic stretch with >99% viable adherent human MSC. MSCs on collagen sheets demonstrated a significantly increased mRNA but not protein expression of SMC markers, compared to on culture flasks. However, cyclic stretch of MSCs on collagen sheets significantly increased both mRNA and protein expression of α-smooth muscle actin, transgelin, and calponin versus plastic and non-stretched sheets. Thus, lineage-specific stiffness and cyclic stretch can be applied together for inducing MSC differentiation towards SMCs without the addition of recombinant growth factors or other soluble factors. This represents a novel stimulation method for modulating the phenotype of MSCs towards SMCs that could easily be incorporated into currently available methodologies to obtain a more targeted control of MSC phenotype.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075785/
_version_	1613694009834733568

Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition

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