Adipose stromal cells differentiation toward smooth muscle cell phenotype diminishes their vasculogenic activity due to induction of activin A secretion

Stephanie Merfeld-Clauss, Benjamin R. Lease, Hongyan Lu, Keith L. March, Dmitry Traktuev

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3 Citations (Scopus)

Abstract

Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs' SMC-lineage commitment affects their subsequent communication with ECs is unknown. The vasculogenic characteristics of human ASCs in progenitor stage and after differentiation towards SMC phenotype were analysed in the present study. Exposure to transforming growth factor β1 (TGFβ1) or activin A has induced expression of SMC markers in ASCs. Analysis performed after treatment withdrawal revealed that secretome of pre-differentiated ASCs had a reduced potency to support EC survival and these ASCs had diminished ability to support EC vasculogenesis in vitro. Vascularization of subcutaneous implants carrying a mixture of ECs and ASCs was 50% lower when, instead of control, pre-differentiated ASCs were used. Pre-differentiated ASCs had an inferior mitogenic response to EC-produced factors. Differentiation of ASCs was accompanied by upregulation of vascular endothelial growth factor and a decrease in hepatocyte growth factor (HGF) production; however, addition of HGF to the co-culture incubation media did not improve vasculogenesis. In parallel, ASC treatment with TGFβ1 induced secretion of activin A. Augmenting co-culture incubation media with anti-activin A IgG restored the ability of pre-differentiated ASCs to support vasculogenesis to the same degree as control ASCs. The present study suggests that TGFβ1 or activin A-induced ASC commitment to SMC phenotype negatively affects the ability of ASCs to support EC vasculogenesis in applications based on EC and ASC co-injection into target tissues.

Original languageEnglish (US)
JournalJournal of Tissue Engineering and Regenerative Medicine
DOIs
StateAccepted/In press - 2016

Fingerprint

Endothelial cells
Stromal Cells
Smooth Muscle Myocytes
Muscle
Cell Differentiation
Cells
Phenotype
Transforming Growth Factors
Hepatocyte Growth Factor
Culture Media
Endothelial Cells
Aptitude
Communication
Vascular Endothelial Growth Factor A
activin A
Intercellular Signaling Peptides and Proteins
Immunoglobulin G
Coculture Techniques
Tissue
Cell Lineage

Keywords

  • Activin A
  • Adipose stromal cells
  • Co-culture
  • Endothelial cells
  • Mural cells
  • Vasculogenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

Cite this

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title = "Adipose stromal cells differentiation toward smooth muscle cell phenotype diminishes their vasculogenic activity due to induction of activin A secretion",
abstract = "Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs' SMC-lineage commitment affects their subsequent communication with ECs is unknown. The vasculogenic characteristics of human ASCs in progenitor stage and after differentiation towards SMC phenotype were analysed in the present study. Exposure to transforming growth factor β1 (TGFβ1) or activin A has induced expression of SMC markers in ASCs. Analysis performed after treatment withdrawal revealed that secretome of pre-differentiated ASCs had a reduced potency to support EC survival and these ASCs had diminished ability to support EC vasculogenesis in vitro. Vascularization of subcutaneous implants carrying a mixture of ECs and ASCs was 50{\%} lower when, instead of control, pre-differentiated ASCs were used. Pre-differentiated ASCs had an inferior mitogenic response to EC-produced factors. Differentiation of ASCs was accompanied by upregulation of vascular endothelial growth factor and a decrease in hepatocyte growth factor (HGF) production; however, addition of HGF to the co-culture incubation media did not improve vasculogenesis. In parallel, ASC treatment with TGFβ1 induced secretion of activin A. Augmenting co-culture incubation media with anti-activin A IgG restored the ability of pre-differentiated ASCs to support vasculogenesis to the same degree as control ASCs. The present study suggests that TGFβ1 or activin A-induced ASC commitment to SMC phenotype negatively affects the ability of ASCs to support EC vasculogenesis in applications based on EC and ASC co-injection into target tissues.",
keywords = "Activin A, Adipose stromal cells, Co-culture, Endothelial cells, Mural cells, Vasculogenesis",
author = "Stephanie Merfeld-Clauss and Lease, {Benjamin R.} and Hongyan Lu and March, {Keith L.} and Dmitry Traktuev",
year = "2016",
doi = "10.1002/term.2223",
language = "English (US)",
journal = "Journal of Tissue Engineering and Regenerative Medicine",
issn = "1932-6254",
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TY - JOUR

T1 - Adipose stromal cells differentiation toward smooth muscle cell phenotype diminishes their vasculogenic activity due to induction of activin A secretion

AU - Merfeld-Clauss, Stephanie

AU - Lease, Benjamin R.

AU - Lu, Hongyan

AU - March, Keith L.

AU - Traktuev, Dmitry

PY - 2016

Y1 - 2016

N2 - Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs' SMC-lineage commitment affects their subsequent communication with ECs is unknown. The vasculogenic characteristics of human ASCs in progenitor stage and after differentiation towards SMC phenotype were analysed in the present study. Exposure to transforming growth factor β1 (TGFβ1) or activin A has induced expression of SMC markers in ASCs. Analysis performed after treatment withdrawal revealed that secretome of pre-differentiated ASCs had a reduced potency to support EC survival and these ASCs had diminished ability to support EC vasculogenesis in vitro. Vascularization of subcutaneous implants carrying a mixture of ECs and ASCs was 50% lower when, instead of control, pre-differentiated ASCs were used. Pre-differentiated ASCs had an inferior mitogenic response to EC-produced factors. Differentiation of ASCs was accompanied by upregulation of vascular endothelial growth factor and a decrease in hepatocyte growth factor (HGF) production; however, addition of HGF to the co-culture incubation media did not improve vasculogenesis. In parallel, ASC treatment with TGFβ1 induced secretion of activin A. Augmenting co-culture incubation media with anti-activin A IgG restored the ability of pre-differentiated ASCs to support vasculogenesis to the same degree as control ASCs. The present study suggests that TGFβ1 or activin A-induced ASC commitment to SMC phenotype negatively affects the ability of ASCs to support EC vasculogenesis in applications based on EC and ASC co-injection into target tissues.

AB - Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs' SMC-lineage commitment affects their subsequent communication with ECs is unknown. The vasculogenic characteristics of human ASCs in progenitor stage and after differentiation towards SMC phenotype were analysed in the present study. Exposure to transforming growth factor β1 (TGFβ1) or activin A has induced expression of SMC markers in ASCs. Analysis performed after treatment withdrawal revealed that secretome of pre-differentiated ASCs had a reduced potency to support EC survival and these ASCs had diminished ability to support EC vasculogenesis in vitro. Vascularization of subcutaneous implants carrying a mixture of ECs and ASCs was 50% lower when, instead of control, pre-differentiated ASCs were used. Pre-differentiated ASCs had an inferior mitogenic response to EC-produced factors. Differentiation of ASCs was accompanied by upregulation of vascular endothelial growth factor and a decrease in hepatocyte growth factor (HGF) production; however, addition of HGF to the co-culture incubation media did not improve vasculogenesis. In parallel, ASC treatment with TGFβ1 induced secretion of activin A. Augmenting co-culture incubation media with anti-activin A IgG restored the ability of pre-differentiated ASCs to support vasculogenesis to the same degree as control ASCs. The present study suggests that TGFβ1 or activin A-induced ASC commitment to SMC phenotype negatively affects the ability of ASCs to support EC vasculogenesis in applications based on EC and ASC co-injection into target tissues.

KW - Activin A

KW - Adipose stromal cells

KW - Co-culture

KW - Endothelial cells

KW - Mural cells

KW - Vasculogenesis

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U2 - 10.1002/term.2223

DO - 10.1002/term.2223

M3 - Article

JO - Journal of Tissue Engineering and Regenerative Medicine

JF - Journal of Tissue Engineering and Regenerative Medicine

SN - 1932-6254

ER -