Adult venous endothelium is a niche for highly proliferative and vasculogenic endothelial colony-forming cells

Linden Green, Richard H. Ofstein, Brian Rapp, M. Reza Saadatzadeh, Janak R. Bhavsar, Andres Fajardo, Michael Dalsing, David Ingram, Michael Murphy

Research output: Contribution to journalArticle

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Abstract

Objective: Postnatal resident endothelium of blood vessels has been proposed to represent terminally differentiated tissue that does not replicate. We previously isolated endothelial colony-forming cells (ECFCs) from human umbilical cord blood (CB) and term placenta by using colony-forming assays and immunocytochemistry. We showed that ECFCs are highly proliferative and form functioning vessels in vivo, the defining characteristics of a true endothelial progenitor cell. This exploratory investigation was conducted to determine whether the endothelium of healthy adult blood vessels contained resident ECFCs. Methods: The endothelium of great saphenous vein (GSV) obtained from vein stripping procedures was collected with mechanical scraping, and ECFCs were isolated according to established protocols. Results: GSV ECFCs incorporated acetylated low-density lipoprotein, formed tubules in Matrigel (BD Biosciences, San Jose, Calif) at 24 hours, and expressed endothelial antigens cluster of differentiation (CD) 144, CD31, CD105, and kinase insert domain receptor but not hematopoietic antigen CD45. Using cumulative population doublings and single-cell assays, we demonstrated that GSV ECFCs exhibited comparable proliferative capacities compared with CB ECFCs, including similar numbers of highly proliferative cells. When injected in collagen/fibronectin gels implanted in nonobese diabetic/severe combined immune deficiency mice, GSV ECFCs formed blood vessels with circulating murine red blood cells, demonstrating their vasculogenic potential. Conclusions: The ECFCs of the GSV contain a hierarchy of progenitor cells with a comparable number of highly proliferative clones as ECFCs of CB. The results of this investigation demonstrate that the adult endothelium contains resident progenitor cells that may have a critical role in vascular homeostasis and repair and could potentially be used as a source of autologous cells for cell therapies focusing on vasculogenesis.

Original languageEnglish (US)
JournalJournal of Vascular Surgery
DOIs
StateAccepted/In press - 2017

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Endothelium
Saphenous Vein
Blood Vessels
Fetal Blood
Stem Cells
CD Antigens
CD45 Antigens
Severe Combined Immunodeficiency
Vascular Endothelial Growth Factor Receptor-2
Cell- and Tissue-Based Therapy
Fibronectins
Placenta
Veins
Homeostasis
Collagen
Clone Cells
Erythrocytes
Gels
Immunohistochemistry

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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Adult venous endothelium is a niche for highly proliferative and vasculogenic endothelial colony-forming cells. / Green, Linden; Ofstein, Richard H.; Rapp, Brian; Saadatzadeh, M. Reza; Bhavsar, Janak R.; Fajardo, Andres; Dalsing, Michael; Ingram, David; Murphy, Michael.

In: Journal of Vascular Surgery, 2017.

Research output: Contribution to journalArticle

Green, Linden ; Ofstein, Richard H. ; Rapp, Brian ; Saadatzadeh, M. Reza ; Bhavsar, Janak R. ; Fajardo, Andres ; Dalsing, Michael ; Ingram, David ; Murphy, Michael. / Adult venous endothelium is a niche for highly proliferative and vasculogenic endothelial colony-forming cells. In: Journal of Vascular Surgery. 2017.
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abstract = "Objective: Postnatal resident endothelium of blood vessels has been proposed to represent terminally differentiated tissue that does not replicate. We previously isolated endothelial colony-forming cells (ECFCs) from human umbilical cord blood (CB) and term placenta by using colony-forming assays and immunocytochemistry. We showed that ECFCs are highly proliferative and form functioning vessels in vivo, the defining characteristics of a true endothelial progenitor cell. This exploratory investigation was conducted to determine whether the endothelium of healthy adult blood vessels contained resident ECFCs. Methods: The endothelium of great saphenous vein (GSV) obtained from vein stripping procedures was collected with mechanical scraping, and ECFCs were isolated according to established protocols. Results: GSV ECFCs incorporated acetylated low-density lipoprotein, formed tubules in Matrigel (BD Biosciences, San Jose, Calif) at 24 hours, and expressed endothelial antigens cluster of differentiation (CD) 144, CD31, CD105, and kinase insert domain receptor but not hematopoietic antigen CD45. Using cumulative population doublings and single-cell assays, we demonstrated that GSV ECFCs exhibited comparable proliferative capacities compared with CB ECFCs, including similar numbers of highly proliferative cells. When injected in collagen/fibronectin gels implanted in nonobese diabetic/severe combined immune deficiency mice, GSV ECFCs formed blood vessels with circulating murine red blood cells, demonstrating their vasculogenic potential. Conclusions: The ECFCs of the GSV contain a hierarchy of progenitor cells with a comparable number of highly proliferative clones as ECFCs of CB. The results of this investigation demonstrate that the adult endothelium contains resident progenitor cells that may have a critical role in vascular homeostasis and repair and could potentially be used as a source of autologous cells for cell therapies focusing on vasculogenesis.",
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AU - Green, Linden

AU - Ofstein, Richard H.

AU - Rapp, Brian

AU - Saadatzadeh, M. Reza

AU - Bhavsar, Janak R.

AU - Fajardo, Andres

AU - Dalsing, Michael

AU - Ingram, David

AU - Murphy, Michael

PY - 2017

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N2 - Objective: Postnatal resident endothelium of blood vessels has been proposed to represent terminally differentiated tissue that does not replicate. We previously isolated endothelial colony-forming cells (ECFCs) from human umbilical cord blood (CB) and term placenta by using colony-forming assays and immunocytochemistry. We showed that ECFCs are highly proliferative and form functioning vessels in vivo, the defining characteristics of a true endothelial progenitor cell. This exploratory investigation was conducted to determine whether the endothelium of healthy adult blood vessels contained resident ECFCs. Methods: The endothelium of great saphenous vein (GSV) obtained from vein stripping procedures was collected with mechanical scraping, and ECFCs were isolated according to established protocols. Results: GSV ECFCs incorporated acetylated low-density lipoprotein, formed tubules in Matrigel (BD Biosciences, San Jose, Calif) at 24 hours, and expressed endothelial antigens cluster of differentiation (CD) 144, CD31, CD105, and kinase insert domain receptor but not hematopoietic antigen CD45. Using cumulative population doublings and single-cell assays, we demonstrated that GSV ECFCs exhibited comparable proliferative capacities compared with CB ECFCs, including similar numbers of highly proliferative cells. When injected in collagen/fibronectin gels implanted in nonobese diabetic/severe combined immune deficiency mice, GSV ECFCs formed blood vessels with circulating murine red blood cells, demonstrating their vasculogenic potential. Conclusions: The ECFCs of the GSV contain a hierarchy of progenitor cells with a comparable number of highly proliferative clones as ECFCs of CB. The results of this investigation demonstrate that the adult endothelium contains resident progenitor cells that may have a critical role in vascular homeostasis and repair and could potentially be used as a source of autologous cells for cell therapies focusing on vasculogenesis.

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