Adipose stromal cells differentiate along a smooth muscle lineage pathway upon endothelial cell contact via induction of activin A

Stephanie Merfeld-Clauss, Ivan P. Lupov, Hongyan Lu, Dongni Feng, Peter Compton-Craig, Keith L. March, Dmitry Traktuev

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Rationale: Adipose stromal cells (ASC) are therapeutically potent progenitor cells that possess properties of pericytes. In vivo, ASC in combination with endothelial cells (EC) establish functional multilayer vessels, in which ASC form the outer vessel layer and differentiate into mural cells. Objective: To identify factors responsible for ASC differentiation toward the smooth muscle cell phenotype via interaction with EC. Methods and Results: An in vitro model of EC cocultivation with ASC was used, in which EC organized into vascular cords, accompanied by ASC migration toward EC and upregulation of α-smooth muscle actin, SM22α, and calponin expression. Conditioned media from EC-ASC, but not from EC cultures, induced smooth muscle cell protein expression in ASC monocultures. EC-ASC cocultivation induced marked accumulation of activin A but not transforming growth factor-β1 in conditioned media. This was attributed to induction of activin A expression in ASC on contact with EC. Although transforming growth factor-β and activin A were individually sufficient to initiate expression of smooth muscle cell antigens in ASC, only activin A IgG blocked the effect of EC-ASC conditioned media. Although transforming growth factor-β was able to induce activin A expression in ASC, in cocultures this induction was transforming growth factor-β independent. In EC-ASC cocultures, activin A IgG or ALK4/5/7 receptor inhibitors blocked expression of α-smooth muscle actin in ASC in the absence of direct ECcord contact, but this inhibition was circumvented in ASC by direct EC contact. Conclusions: EC initiate a smooth muscle cell differentiation program in adjacent ASC and propagate this differentiation in distant ASC by induction of activin A expression. (Circ Res. 2014;115:800-809.)

Original languageEnglish
Pages (from-to)800-809
Number of pages10
JournalCirculation Research
Volume115
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Stromal Cells
Smooth Muscle
Endothelial Cells
Transforming Growth Factors
Coculture Techniques
Smooth Muscle Myocytes
Conditioned Culture Medium
activin A
Cell Differentiation
Actins
Immunoglobulin G
Contact Inhibition
Pericytes
Muscle Proteins

Keywords

  • Activin A
  • Adipose tissue
  • Coculture techniques
  • Endothelial cells
  • Mesenchymal stem cells
  • Neovascularization
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Adipose stromal cells differentiate along a smooth muscle lineage pathway upon endothelial cell contact via induction of activin A. / Merfeld-Clauss, Stephanie; Lupov, Ivan P.; Lu, Hongyan; Feng, Dongni; Compton-Craig, Peter; March, Keith L.; Traktuev, Dmitry.

In: Circulation Research, Vol. 115, No. 9, 2014, p. 800-809.

Research output: Contribution to journalArticle

Merfeld-Clauss, Stephanie ; Lupov, Ivan P. ; Lu, Hongyan ; Feng, Dongni ; Compton-Craig, Peter ; March, Keith L. ; Traktuev, Dmitry. / Adipose stromal cells differentiate along a smooth muscle lineage pathway upon endothelial cell contact via induction of activin A. In: Circulation Research. 2014 ; Vol. 115, No. 9. pp. 800-809.
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abstract = "Rationale: Adipose stromal cells (ASC) are therapeutically potent progenitor cells that possess properties of pericytes. In vivo, ASC in combination with endothelial cells (EC) establish functional multilayer vessels, in which ASC form the outer vessel layer and differentiate into mural cells. Objective: To identify factors responsible for ASC differentiation toward the smooth muscle cell phenotype via interaction with EC. Methods and Results: An in vitro model of EC cocultivation with ASC was used, in which EC organized into vascular cords, accompanied by ASC migration toward EC and upregulation of α-smooth muscle actin, SM22α, and calponin expression. Conditioned media from EC-ASC, but not from EC cultures, induced smooth muscle cell protein expression in ASC monocultures. EC-ASC cocultivation induced marked accumulation of activin A but not transforming growth factor-β1 in conditioned media. This was attributed to induction of activin A expression in ASC on contact with EC. Although transforming growth factor-β and activin A were individually sufficient to initiate expression of smooth muscle cell antigens in ASC, only activin A IgG blocked the effect of EC-ASC conditioned media. Although transforming growth factor-β was able to induce activin A expression in ASC, in cocultures this induction was transforming growth factor-β independent. In EC-ASC cocultures, activin A IgG or ALK4/5/7 receptor inhibitors blocked expression of α-smooth muscle actin in ASC in the absence of direct ECcord contact, but this inhibition was circumvented in ASC by direct EC contact. Conclusions: EC initiate a smooth muscle cell differentiation program in adjacent ASC and propagate this differentiation in distant ASC by induction of activin A expression. (Circ Res. 2014;115:800-809.)",
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T1 - Adipose stromal cells differentiate along a smooth muscle lineage pathway upon endothelial cell contact via induction of activin A

AU - Merfeld-Clauss, Stephanie

AU - Lupov, Ivan P.

AU - Lu, Hongyan

AU - Feng, Dongni

AU - Compton-Craig, Peter

AU - March, Keith L.

AU - Traktuev, Dmitry

PY - 2014

Y1 - 2014

N2 - Rationale: Adipose stromal cells (ASC) are therapeutically potent progenitor cells that possess properties of pericytes. In vivo, ASC in combination with endothelial cells (EC) establish functional multilayer vessels, in which ASC form the outer vessel layer and differentiate into mural cells. Objective: To identify factors responsible for ASC differentiation toward the smooth muscle cell phenotype via interaction with EC. Methods and Results: An in vitro model of EC cocultivation with ASC was used, in which EC organized into vascular cords, accompanied by ASC migration toward EC and upregulation of α-smooth muscle actin, SM22α, and calponin expression. Conditioned media from EC-ASC, but not from EC cultures, induced smooth muscle cell protein expression in ASC monocultures. EC-ASC cocultivation induced marked accumulation of activin A but not transforming growth factor-β1 in conditioned media. This was attributed to induction of activin A expression in ASC on contact with EC. Although transforming growth factor-β and activin A were individually sufficient to initiate expression of smooth muscle cell antigens in ASC, only activin A IgG blocked the effect of EC-ASC conditioned media. Although transforming growth factor-β was able to induce activin A expression in ASC, in cocultures this induction was transforming growth factor-β independent. In EC-ASC cocultures, activin A IgG or ALK4/5/7 receptor inhibitors blocked expression of α-smooth muscle actin in ASC in the absence of direct ECcord contact, but this inhibition was circumvented in ASC by direct EC contact. Conclusions: EC initiate a smooth muscle cell differentiation program in adjacent ASC and propagate this differentiation in distant ASC by induction of activin A expression. (Circ Res. 2014;115:800-809.)

AB - Rationale: Adipose stromal cells (ASC) are therapeutically potent progenitor cells that possess properties of pericytes. In vivo, ASC in combination with endothelial cells (EC) establish functional multilayer vessels, in which ASC form the outer vessel layer and differentiate into mural cells. Objective: To identify factors responsible for ASC differentiation toward the smooth muscle cell phenotype via interaction with EC. Methods and Results: An in vitro model of EC cocultivation with ASC was used, in which EC organized into vascular cords, accompanied by ASC migration toward EC and upregulation of α-smooth muscle actin, SM22α, and calponin expression. Conditioned media from EC-ASC, but not from EC cultures, induced smooth muscle cell protein expression in ASC monocultures. EC-ASC cocultivation induced marked accumulation of activin A but not transforming growth factor-β1 in conditioned media. This was attributed to induction of activin A expression in ASC on contact with EC. Although transforming growth factor-β and activin A were individually sufficient to initiate expression of smooth muscle cell antigens in ASC, only activin A IgG blocked the effect of EC-ASC conditioned media. Although transforming growth factor-β was able to induce activin A expression in ASC, in cocultures this induction was transforming growth factor-β independent. In EC-ASC cocultures, activin A IgG or ALK4/5/7 receptor inhibitors blocked expression of α-smooth muscle actin in ASC in the absence of direct ECcord contact, but this inhibition was circumvented in ASC by direct EC contact. Conclusions: EC initiate a smooth muscle cell differentiation program in adjacent ASC and propagate this differentiation in distant ASC by induction of activin A expression. (Circ Res. 2014;115:800-809.)

KW - Activin A

KW - Adipose tissue

KW - Coculture techniques

KW - Endothelial cells

KW - Mesenchymal stem cells

KW - Neovascularization

KW - Smooth muscle

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DO - 10.1161/CIRCRESAHA.115.304026

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