Skin graft vascularization involves precisely regulated regression and replacement of endothelial cells through both angiogenesis and vasculogenesis

Jennifer M. Capla, Daniel J. Ceradini, Oren M. Tepper, Matthew J. Callaghan, Kirit A. Bhatt, Robert D. Galiano, Jamie P. Levine, Geoffrey C. Gurtner

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Long-term survival of a skin graft is dependent on eventual revascularization. The authors' aim in the present study was to determine whether skin graft vascularization occurs by (1) simple reconnection of vessels, (2) ingrowth of recipient vasculature, (3) outgrowth of donor-derived vessels, and/or (4) recruitment of bone marrow-derived endothelial progenitor cells. METHODS: Full-thickness skin grafts (1 × 1 cm) were transferred between wild-type FVB/N mice (n = 20) and transgenic tie2/lacZ mice (n = 20), where lacZ expression is controlled by the endothelial specific tie2 promoter, allowing differentiation of recipient and donor endothelial cells. The contribution of endothelial progenitor cells to skin graft neovascularization was determined using a bone marrow transplant model where tie2/lacZ bone marrow was transplanted into wild-type mice (n = 20). RESULTS: Vascular regression in the graft was observed at the periphery starting on day 3 and moving centrally through day 21, sparing graft vessels in the absolute center of the graft. At the same time, vascular ingrowth occurred from the wound bed to replace the regressing vessels. Furthermore, bone marrow-derived endothelial progenitor cells contributed to these new vessels starting as early as day 7. Surprisingly, the contribution of bone marrow-derived vessels to the overall process was approximately 15 to 20 percent of new endothelial cells. CONCLUSIONS: Replacement of the donor graft vasculature by endothelial and endothelial progenitor cells from the recipient along preexisting channels is the predominant mechanism for skin graft revascularization. This mechanism is likely similar for all nonvascularized free grafts and suggests novel strategies for optimizing the vascularization of tissue constructs engineered in vitro.

Original languageEnglish (US)
Pages (from-to)836-844
Number of pages9
JournalPlastic and Reconstructive Surgery
Volume117
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

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Endothelial Cells
Transplants
Skin
Bone Marrow
Blood Vessels
Endothelial Progenitor Cells
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery

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Skin graft vascularization involves precisely regulated regression and replacement of endothelial cells through both angiogenesis and vasculogenesis. / Capla, Jennifer M.; Ceradini, Daniel J.; Tepper, Oren M.; Callaghan, Matthew J.; Bhatt, Kirit A.; Galiano, Robert D.; Levine, Jamie P.; Gurtner, Geoffrey C.

In: Plastic and Reconstructive Surgery, Vol. 117, No. 3, 03.2006, p. 836-844.

Research output: Contribution to journalArticle

Capla, Jennifer M. ; Ceradini, Daniel J. ; Tepper, Oren M. ; Callaghan, Matthew J. ; Bhatt, Kirit A. ; Galiano, Robert D. ; Levine, Jamie P. ; Gurtner, Geoffrey C. / Skin graft vascularization involves precisely regulated regression and replacement of endothelial cells through both angiogenesis and vasculogenesis. In: Plastic and Reconstructive Surgery. 2006 ; Vol. 117, No. 3. pp. 836-844.
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abstract = "BACKGROUND: Long-term survival of a skin graft is dependent on eventual revascularization. The authors' aim in the present study was to determine whether skin graft vascularization occurs by (1) simple reconnection of vessels, (2) ingrowth of recipient vasculature, (3) outgrowth of donor-derived vessels, and/or (4) recruitment of bone marrow-derived endothelial progenitor cells. METHODS: Full-thickness skin grafts (1 × 1 cm) were transferred between wild-type FVB/N mice (n = 20) and transgenic tie2/lacZ mice (n = 20), where lacZ expression is controlled by the endothelial specific tie2 promoter, allowing differentiation of recipient and donor endothelial cells. The contribution of endothelial progenitor cells to skin graft neovascularization was determined using a bone marrow transplant model where tie2/lacZ bone marrow was transplanted into wild-type mice (n = 20). RESULTS: Vascular regression in the graft was observed at the periphery starting on day 3 and moving centrally through day 21, sparing graft vessels in the absolute center of the graft. At the same time, vascular ingrowth occurred from the wound bed to replace the regressing vessels. Furthermore, bone marrow-derived endothelial progenitor cells contributed to these new vessels starting as early as day 7. Surprisingly, the contribution of bone marrow-derived vessels to the overall process was approximately 15 to 20 percent of new endothelial cells. CONCLUSIONS: Replacement of the donor graft vasculature by endothelial and endothelial progenitor cells from the recipient along preexisting channels is the predominant mechanism for skin graft revascularization. This mechanism is likely similar for all nonvascularized free grafts and suggests novel strategies for optimizing the vascularization of tissue constructs engineered in vitro.",
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T1 - Skin graft vascularization involves precisely regulated regression and replacement of endothelial cells through both angiogenesis and vasculogenesis

AU - Capla, Jennifer M.

AU - Ceradini, Daniel J.

AU - Tepper, Oren M.

AU - Callaghan, Matthew J.

AU - Bhatt, Kirit A.

AU - Galiano, Robert D.

AU - Levine, Jamie P.

AU - Gurtner, Geoffrey C.

PY - 2006/3

Y1 - 2006/3

N2 - BACKGROUND: Long-term survival of a skin graft is dependent on eventual revascularization. The authors' aim in the present study was to determine whether skin graft vascularization occurs by (1) simple reconnection of vessels, (2) ingrowth of recipient vasculature, (3) outgrowth of donor-derived vessels, and/or (4) recruitment of bone marrow-derived endothelial progenitor cells. METHODS: Full-thickness skin grafts (1 × 1 cm) were transferred between wild-type FVB/N mice (n = 20) and transgenic tie2/lacZ mice (n = 20), where lacZ expression is controlled by the endothelial specific tie2 promoter, allowing differentiation of recipient and donor endothelial cells. The contribution of endothelial progenitor cells to skin graft neovascularization was determined using a bone marrow transplant model where tie2/lacZ bone marrow was transplanted into wild-type mice (n = 20). RESULTS: Vascular regression in the graft was observed at the periphery starting on day 3 and moving centrally through day 21, sparing graft vessels in the absolute center of the graft. At the same time, vascular ingrowth occurred from the wound bed to replace the regressing vessels. Furthermore, bone marrow-derived endothelial progenitor cells contributed to these new vessels starting as early as day 7. Surprisingly, the contribution of bone marrow-derived vessels to the overall process was approximately 15 to 20 percent of new endothelial cells. CONCLUSIONS: Replacement of the donor graft vasculature by endothelial and endothelial progenitor cells from the recipient along preexisting channels is the predominant mechanism for skin graft revascularization. This mechanism is likely similar for all nonvascularized free grafts and suggests novel strategies for optimizing the vascularization of tissue constructs engineered in vitro.

AB - BACKGROUND: Long-term survival of a skin graft is dependent on eventual revascularization. The authors' aim in the present study was to determine whether skin graft vascularization occurs by (1) simple reconnection of vessels, (2) ingrowth of recipient vasculature, (3) outgrowth of donor-derived vessels, and/or (4) recruitment of bone marrow-derived endothelial progenitor cells. METHODS: Full-thickness skin grafts (1 × 1 cm) were transferred between wild-type FVB/N mice (n = 20) and transgenic tie2/lacZ mice (n = 20), where lacZ expression is controlled by the endothelial specific tie2 promoter, allowing differentiation of recipient and donor endothelial cells. The contribution of endothelial progenitor cells to skin graft neovascularization was determined using a bone marrow transplant model where tie2/lacZ bone marrow was transplanted into wild-type mice (n = 20). RESULTS: Vascular regression in the graft was observed at the periphery starting on day 3 and moving centrally through day 21, sparing graft vessels in the absolute center of the graft. At the same time, vascular ingrowth occurred from the wound bed to replace the regressing vessels. Furthermore, bone marrow-derived endothelial progenitor cells contributed to these new vessels starting as early as day 7. Surprisingly, the contribution of bone marrow-derived vessels to the overall process was approximately 15 to 20 percent of new endothelial cells. CONCLUSIONS: Replacement of the donor graft vasculature by endothelial and endothelial progenitor cells from the recipient along preexisting channels is the predominant mechanism for skin graft revascularization. This mechanism is likely similar for all nonvascularized free grafts and suggests novel strategies for optimizing the vascularization of tissue constructs engineered in vitro.

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