Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells

Fernando A Fierro, Adam J. O'Neal, Julie R. Beegle, Myra N. Chávez, Thomas R. Peavy, Roslyn Rivkah Isseroff, José T. Egaña

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34 + hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.

Original languageEnglish (US)
Article number68
JournalFrontiers in Cell and Developmental Biology
Volume3
Issue numberOCT
DOIs
StatePublished - Oct 30 2015

Fingerprint

Mesenchymal Stromal Cells
Regeneration
Endothelial Cells
Skin
Serpins
Cell- and Tissue-Based Therapy
Hematopoietic Stem Cells
Interleukin-8
Vascular Endothelial Growth Factor A
Bone Marrow
Wounds and Injuries

Keywords

  • Angiogenesis
  • Hypoxia
  • Mesenchymal stem cells
  • Scaffolds
  • Wound healing

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells. / Fierro, Fernando A; O'Neal, Adam J.; Beegle, Julie R.; Chávez, Myra N.; Peavy, Thomas R.; Isseroff, Roslyn Rivkah; Egaña, José T.

In: Frontiers in Cell and Developmental Biology, Vol. 3, No. OCT, 68, 30.10.2015.

Research output: Contribution to journalArticle

@article{e301ec5d58e84c6b8ae64eb26d5d22ec,
title = "Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells",
abstract = "Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34 + hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.",
keywords = "Angiogenesis, Hypoxia, Mesenchymal stem cells, Scaffolds, Wound healing",
author = "Fierro, {Fernando A} and O'Neal, {Adam J.} and Beegle, {Julie R.} and Ch{\'a}vez, {Myra N.} and Peavy, {Thomas R.} and Isseroff, {Roslyn Rivkah} and Ega{\~n}a, {Jos{\'e} T.}",
year = "2015",
month = "10",
day = "30",
doi = "10.3389/fcell.2015.00068",
language = "English (US)",
volume = "3",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media S. A.",
number = "OCT",

}

TY - JOUR

T1 - Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells

AU - Fierro, Fernando A

AU - O'Neal, Adam J.

AU - Beegle, Julie R.

AU - Chávez, Myra N.

AU - Peavy, Thomas R.

AU - Isseroff, Roslyn Rivkah

AU - Egaña, José T.

PY - 2015/10/30

Y1 - 2015/10/30

N2 - Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34 + hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.

AB - Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34 + hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds.

KW - Angiogenesis

KW - Hypoxia

KW - Mesenchymal stem cells

KW - Scaffolds

KW - Wound healing

UR - http://www.scopus.com/inward/record.url?scp=85021432524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021432524&partnerID=8YFLogxK

U2 - 10.3389/fcell.2015.00068

DO - 10.3389/fcell.2015.00068

M3 - Article

AN - SCOPUS:85021432524

VL - 3

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

SN - 2296-634X

IS - OCT

M1 - 68

ER -