Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells
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 therapie...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fcell.2015.00068/full |
| _version_ | 1811301130024517632 |
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| author | Fernando Antonio Fierro Adam James O'Neal Julie Rose Beegle Myra N Chávez Myra N Chávez Thomas Robert Peavy Roslyn Rivkah Isseroff Tomás eEgana Tomás eEgana Tomás eEgana |
| author_facet | Fernando Antonio Fierro Adam James O'Neal Julie Rose Beegle Myra N Chávez Myra N Chávez Thomas Robert Peavy Roslyn Rivkah Isseroff Tomás eEgana Tomás eEgana Tomás eEgana |
| author_sort | Fernando Antonio Fierro |
| collection | DOAJ |
| description | 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-1 and induce transwell migration of CD34+ hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1 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. |
| first_indexed | 2024-04-13T07:03:25Z |
| format | Article |
| id | doaj.art-8cab5892f13d4cf6bb67304784153c50 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-13T07:03:25Z |
| publishDate | 2015-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-8cab5892f13d4cf6bb67304784153c502022-12-22T02:57:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2015-10-01310.3389/fcell.2015.00068160848Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cellsFernando Antonio Fierro0Adam James O'Neal1Julie Rose Beegle2Myra N Chávez3Myra N Chávez4Thomas Robert Peavy5Roslyn Rivkah Isseroff6Tomás eEgana7Tomás eEgana8Tomás eEgana9University of California DavisCalifornia State University, SacramentoUniversity of California DavisTechnische Universität MünchenFacultad de Ciencias, Universidad de ChileCalifornia State University, SacramentoUniversity of California DavisTechnische Universität MünchenFacultad de Ciencias, Universidad de ChilePontificia Universidad Católica de ChileMany 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-1 and induce transwell migration of CD34+ hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1 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.http://journal.frontiersin.org/Journal/10.3389/fcell.2015.00068/fullMesenchymal Stem CellsWound HealinghypoxiaAngiogenesisscaffolds |
| spellingShingle | Fernando Antonio Fierro Adam James O'Neal Julie Rose Beegle Myra N Chávez Myra N Chávez Thomas Robert Peavy Roslyn Rivkah Isseroff Tomás eEgana Tomás eEgana Tomás eEgana Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells Frontiers in Cell and Developmental Biology Mesenchymal Stem Cells Wound Healing hypoxia Angiogenesis scaffolds |
| title | Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells |
| title_full | Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells |
| title_fullStr | Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells |
| title_full_unstemmed | Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells |
| title_short | Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells |
| title_sort | hypoxic pre conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre seeded with mesenchymal stem cells |
| topic | Mesenchymal Stem Cells Wound Healing hypoxia Angiogenesis scaffolds |
| url | http://journal.frontiersin.org/Journal/10.3389/fcell.2015.00068/full |
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