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  • Ball_et_al-2014-STEM_CELLS

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Mesenchymal stromal cells: inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential

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Mesenchymal stromal cells : inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential. / Ball, S. G.; Worthington, John J.; Canfield, A. E.; Merry, C. L. R.; Kielty, C. M.

In: Stem Cells, Vol. 32, No. 3, 03.2014, p. 694-705.

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Ball, S. G. ; Worthington, John J. ; Canfield, A. E. ; Merry, C. L. R. ; Kielty, C. M. / Mesenchymal stromal cells : inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential. In: Stem Cells. 2014 ; Vol. 32, No. 3. pp. 694-705.

Bibtex

@article{7e4bf4d21ce24b80ad3363e72983e880,
title = "Mesenchymal stromal cells: inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential",
abstract = "Realizing the full therapeutic potential of mesenchymal stromal/stem cells (MSCs) awaits improved understanding of mechanisms controlling their fate. Using MSCs cultured as spheroids to recapitulate a three-dimensional cellular environment, we show that perturbing the mesenchymal regulators, platelet-derived growth factor (PDGF) receptors or fibronectin, reverts MSCs toward mesodermal progenitors with endothelial potential that can potently induce neovascularization in vivo. MSCs within untreated spheroids retain their mesenchymal spindle shape with abundant smooth muscle α-actin filaments and fibronectin-rich matrix. Inhibiting PDGF receptors or depleting fibronectin induces rounding and depletes smooth muscle α-actin expression; these cells have characteristics of mesenchymoangioblasts, with enhanced expression of mesendoderm and endoderm transcription factors, prominent upregulation of E-cadherin, and Janus kinase signaling-dependent expression of Oct4A and Nanog. PDGF receptor-inhibited spheroids also upregulate endothelial markers platelet endothelial cell adhesion molecule 1 and vascular endothelial-cadherin and secrete many angiogenic factors, and in vivo they potently stimulate neovascularization, and their MSCs integrate within functional blood vessels that are perfused by the circulation. Thus, MSC potency and vascular induction are regulated by perturbing mesenchymal fate.",
keywords = "Adult, Angiogenesis Inducing Agents, Animals, Collagen, Drug Combinations, Endothelial Cells, Female, Fibronectins, Gene Expression Profiling, Homeodomain Proteins, Humans, Laminin, Male, Mesenchymal Stromal Cells, Mesoderm, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic, Octamer Transcription Factor-3, Proteoglycans, Receptors, Platelet-Derived Growth Factor, Signal Transduction, Spheroids, Cellular, Up-Regulation, Young Adult",
author = "Ball, {S. G.} and Worthington, {John J.} and Canfield, {A. E.} and Merry, {C. L. R.} and Kielty, {C. M.}",
note = "{\textcopyright} AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.",
year = "2014",
month = mar,
doi = "10.1002/stem.1538",
language = "English",
volume = "32",
pages = "694--705",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",
number = "3",

}

RIS

TY - JOUR

T1 - Mesenchymal stromal cells

T2 - inhibiting PDGF receptors or depleting fibronectin induces mesodermal progenitors with endothelial potential

AU - Ball, S. G.

AU - Worthington, John J.

AU - Canfield, A. E.

AU - Merry, C. L. R.

AU - Kielty, C. M.

N1 - © AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

PY - 2014/3

Y1 - 2014/3

N2 - Realizing the full therapeutic potential of mesenchymal stromal/stem cells (MSCs) awaits improved understanding of mechanisms controlling their fate. Using MSCs cultured as spheroids to recapitulate a three-dimensional cellular environment, we show that perturbing the mesenchymal regulators, platelet-derived growth factor (PDGF) receptors or fibronectin, reverts MSCs toward mesodermal progenitors with endothelial potential that can potently induce neovascularization in vivo. MSCs within untreated spheroids retain their mesenchymal spindle shape with abundant smooth muscle α-actin filaments and fibronectin-rich matrix. Inhibiting PDGF receptors or depleting fibronectin induces rounding and depletes smooth muscle α-actin expression; these cells have characteristics of mesenchymoangioblasts, with enhanced expression of mesendoderm and endoderm transcription factors, prominent upregulation of E-cadherin, and Janus kinase signaling-dependent expression of Oct4A and Nanog. PDGF receptor-inhibited spheroids also upregulate endothelial markers platelet endothelial cell adhesion molecule 1 and vascular endothelial-cadherin and secrete many angiogenic factors, and in vivo they potently stimulate neovascularization, and their MSCs integrate within functional blood vessels that are perfused by the circulation. Thus, MSC potency and vascular induction are regulated by perturbing mesenchymal fate.

AB - Realizing the full therapeutic potential of mesenchymal stromal/stem cells (MSCs) awaits improved understanding of mechanisms controlling their fate. Using MSCs cultured as spheroids to recapitulate a three-dimensional cellular environment, we show that perturbing the mesenchymal regulators, platelet-derived growth factor (PDGF) receptors or fibronectin, reverts MSCs toward mesodermal progenitors with endothelial potential that can potently induce neovascularization in vivo. MSCs within untreated spheroids retain their mesenchymal spindle shape with abundant smooth muscle α-actin filaments and fibronectin-rich matrix. Inhibiting PDGF receptors or depleting fibronectin induces rounding and depletes smooth muscle α-actin expression; these cells have characteristics of mesenchymoangioblasts, with enhanced expression of mesendoderm and endoderm transcription factors, prominent upregulation of E-cadherin, and Janus kinase signaling-dependent expression of Oct4A and Nanog. PDGF receptor-inhibited spheroids also upregulate endothelial markers platelet endothelial cell adhesion molecule 1 and vascular endothelial-cadherin and secrete many angiogenic factors, and in vivo they potently stimulate neovascularization, and their MSCs integrate within functional blood vessels that are perfused by the circulation. Thus, MSC potency and vascular induction are regulated by perturbing mesenchymal fate.

KW - Adult

KW - Angiogenesis Inducing Agents

KW - Animals

KW - Collagen

KW - Drug Combinations

KW - Endothelial Cells

KW - Female

KW - Fibronectins

KW - Gene Expression Profiling

KW - Homeodomain Proteins

KW - Humans

KW - Laminin

KW - Male

KW - Mesenchymal Stromal Cells

KW - Mesoderm

KW - Mice

KW - Mice, Inbred C57BL

KW - Neovascularization, Physiologic

KW - Octamer Transcription Factor-3

KW - Proteoglycans

KW - Receptors, Platelet-Derived Growth Factor

KW - Signal Transduction

KW - Spheroids, Cellular

KW - Up-Regulation

KW - Young Adult

U2 - 10.1002/stem.1538

DO - 10.1002/stem.1538

M3 - Journal article

C2 - 24022915

VL - 32

SP - 694

EP - 705

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 3

ER -