γ-Irradiated cord blood MNCs: Different paracrine effects on mature and progenitor endothelial cells

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Abstract

Cell-based therapies have been employed to promote neovascularization mainly through the release of paracrine factors inhibiting apoptosis and supporting migration and proliferation of resident differentiated cells. We tested in vitro pro-angiogenic effects of apoptotic cord blood-derived mononuclear cells (CB-MNCs) and their conditioned medium (CM) on mature endothelial cells (HUVECs) and peripheral blood-derived endothelial progenitor cells (ECFCs).CB-MNCs were γ-irradiated to induce apoptosis and cultured for 72. h to obtain the release of CM. MNCs viability, evaluated by flow cytometry, decreased progressively after γ-irradiation reaching 41% at 72. h. γ-Irradiated MNCs (γMNCs) released increasing amounts of EGF, PDGF-AB and VEGF in their CM over time, as assessed by ELISA. γ-MNCs and their CM enhanced capillary-like network formation (in a dose-dependent and time-persistent manner), proliferation and migration of HUVECs in vitro, while they primed capillary-like network formation (dose-independent and not time-persistent) and induced migration but did not support proliferation of ECFCs. Our data support the hypothesis of paracrine mechanism as prevalent in regenerative medicine and demonstrate the efficacy of MNCs secretome in inducing neovascularization. To our knowledge, this is the first paper highlighting differential pro-angiogenic effects of CM on mature and progenitor endothelial cells, adding a tile in the understanding of mechanisms involved in neovascularization.

Original languageEnglish
Pages (from-to)9-16
Number of pages8
JournalMicrovascular Research
Volume94
DOIs
Publication statusPublished - 2014

Fingerprint

Endothelial cells
Conditioned Culture Medium
Fetal Blood
Blood
Apoptosis
Regenerative Medicine
Flow cytometry
Tile
Cell- and Tissue-Based Therapy
Epidermal Growth Factor
Vascular Endothelial Growth Factor A
Flow Cytometry
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Endothelial Progenitor Cells
Irradiation
In Vitro Techniques

Keywords

  • Conditioned medium
  • Cord blood
  • Endothelial cells
  • Endothelial progenitor cells
  • Mononuclear cells
  • Neovascularization

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology
  • Medicine(all)

Cite this

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title = "γ-Irradiated cord blood MNCs: Different paracrine effects on mature and progenitor endothelial cells",
abstract = "Cell-based therapies have been employed to promote neovascularization mainly through the release of paracrine factors inhibiting apoptosis and supporting migration and proliferation of resident differentiated cells. We tested in vitro pro-angiogenic effects of apoptotic cord blood-derived mononuclear cells (CB-MNCs) and their conditioned medium (CM) on mature endothelial cells (HUVECs) and peripheral blood-derived endothelial progenitor cells (ECFCs).CB-MNCs were γ-irradiated to induce apoptosis and cultured for 72. h to obtain the release of CM. MNCs viability, evaluated by flow cytometry, decreased progressively after γ-irradiation reaching 41{\%} at 72. h. γ-Irradiated MNCs (γMNCs) released increasing amounts of EGF, PDGF-AB and VEGF in their CM over time, as assessed by ELISA. γ-MNCs and their CM enhanced capillary-like network formation (in a dose-dependent and time-persistent manner), proliferation and migration of HUVECs in vitro, while they primed capillary-like network formation (dose-independent and not time-persistent) and induced migration but did not support proliferation of ECFCs. Our data support the hypothesis of paracrine mechanism as prevalent in regenerative medicine and demonstrate the efficacy of MNCs secretome in inducing neovascularization. To our knowledge, this is the first paper highlighting differential pro-angiogenic effects of CM on mature and progenitor endothelial cells, adding a tile in the understanding of mechanisms involved in neovascularization.",
keywords = "Conditioned medium, Cord blood, Endothelial cells, Endothelial progenitor cells, Mononuclear cells, Neovascularization",
author = "Marila Cervio and Luigia Scudeller and Gianluca Viarengo and Manuela Monti and {Del Fante}, Claudia and Vittorio Arici and Cesare Perotti",
year = "2014",
doi = "10.1016/j.mvr.2014.04.009",
language = "English",
volume = "94",
pages = "9--16",
journal = "Microvascular Research",
issn = "0026-2862",
publisher = "Academic Press Inc.",

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TY - JOUR

T1 - γ-Irradiated cord blood MNCs

T2 - Different paracrine effects on mature and progenitor endothelial cells

AU - Cervio, Marila

AU - Scudeller, Luigia

AU - Viarengo, Gianluca

AU - Monti, Manuela

AU - Del Fante, Claudia

AU - Arici, Vittorio

AU - Perotti, Cesare

PY - 2014

Y1 - 2014

N2 - Cell-based therapies have been employed to promote neovascularization mainly through the release of paracrine factors inhibiting apoptosis and supporting migration and proliferation of resident differentiated cells. We tested in vitro pro-angiogenic effects of apoptotic cord blood-derived mononuclear cells (CB-MNCs) and their conditioned medium (CM) on mature endothelial cells (HUVECs) and peripheral blood-derived endothelial progenitor cells (ECFCs).CB-MNCs were γ-irradiated to induce apoptosis and cultured for 72. h to obtain the release of CM. MNCs viability, evaluated by flow cytometry, decreased progressively after γ-irradiation reaching 41% at 72. h. γ-Irradiated MNCs (γMNCs) released increasing amounts of EGF, PDGF-AB and VEGF in their CM over time, as assessed by ELISA. γ-MNCs and their CM enhanced capillary-like network formation (in a dose-dependent and time-persistent manner), proliferation and migration of HUVECs in vitro, while they primed capillary-like network formation (dose-independent and not time-persistent) and induced migration but did not support proliferation of ECFCs. Our data support the hypothesis of paracrine mechanism as prevalent in regenerative medicine and demonstrate the efficacy of MNCs secretome in inducing neovascularization. To our knowledge, this is the first paper highlighting differential pro-angiogenic effects of CM on mature and progenitor endothelial cells, adding a tile in the understanding of mechanisms involved in neovascularization.

AB - Cell-based therapies have been employed to promote neovascularization mainly through the release of paracrine factors inhibiting apoptosis and supporting migration and proliferation of resident differentiated cells. We tested in vitro pro-angiogenic effects of apoptotic cord blood-derived mononuclear cells (CB-MNCs) and their conditioned medium (CM) on mature endothelial cells (HUVECs) and peripheral blood-derived endothelial progenitor cells (ECFCs).CB-MNCs were γ-irradiated to induce apoptosis and cultured for 72. h to obtain the release of CM. MNCs viability, evaluated by flow cytometry, decreased progressively after γ-irradiation reaching 41% at 72. h. γ-Irradiated MNCs (γMNCs) released increasing amounts of EGF, PDGF-AB and VEGF in their CM over time, as assessed by ELISA. γ-MNCs and their CM enhanced capillary-like network formation (in a dose-dependent and time-persistent manner), proliferation and migration of HUVECs in vitro, while they primed capillary-like network formation (dose-independent and not time-persistent) and induced migration but did not support proliferation of ECFCs. Our data support the hypothesis of paracrine mechanism as prevalent in regenerative medicine and demonstrate the efficacy of MNCs secretome in inducing neovascularization. To our knowledge, this is the first paper highlighting differential pro-angiogenic effects of CM on mature and progenitor endothelial cells, adding a tile in the understanding of mechanisms involved in neovascularization.

KW - Conditioned medium

KW - Cord blood

KW - Endothelial cells

KW - Endothelial progenitor cells

KW - Mononuclear cells

KW - Neovascularization

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