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Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

Koob TJ, Lim JJ, Massee M, Zabek N, Rennert R, Gurtner G, Li WW - (2014)

Bottom Line: Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro.Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process.TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

View Article: PubMed Central - HTML - PubMed

Affiliation: MiMedx Group, Inc., 1775 West Oak Commons Ct., Marietta, GA, USA.

ABSTRACT

Background: Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis.

Methods: Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model.

Results: Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process.

Conclusions: TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

No MeSH data available.


Related in: MedlinePlus

Change in growth factor production by human microvascular endothelial cells when cultured in the presence of varying concentrations of dHACM extract. Endothelial cells increased production of a number of angiogenic factors when cultured in the presence of dHACM extract, compared to untreated cells cultured without extract (green/blue). A few regulatory factors were also down regulated in the presence of extract (red/yellow), while many factors remained unchanged (black), relative to untreated controls.
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Figure 2: Change in growth factor production by human microvascular endothelial cells when cultured in the presence of varying concentrations of dHACM extract. Endothelial cells increased production of a number of angiogenic factors when cultured in the presence of dHACM extract, compared to untreated cells cultured without extract (green/blue). A few regulatory factors were also down regulated in the presence of extract (red/yellow), while many factors remained unchanged (black), relative to untreated controls.

Mentions: The induction of specific growth factor production by endothelial cells in culture caused by extracts of dHACM is shown in Figure 2. HMVECs greatly increased production of a number of angiogenic factors including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, TGF-β3, HB-EGF, and interleukin-2 (IL-2) when cultured in the presence of dHACM extract, compared to untreated cells cultured without extract (Figure 2, green). HMVECs also increased production of molecules such as IL-6, angiogenin, and PDGF-BB to a lesser degree in the presence of extract (Figure 2, blue). A few regulatory factors including tumor necrosis factor α (TNF-α) and IL-10 were down regulated in the presence of extract (Figure 2, red/yellow), while many factors such as bFGF, HGF, and TGF-β1 remained unchanged (black), relative to untreated controls.


Angiogenic properties of dehydrated human amnion/chorion allografts: therapeutic potential for soft tissue repair and regeneration.

Koob TJ, Lim JJ, Massee M, Zabek N, Rennert R, Gurtner G, Li WW - (2014)

Change in growth factor production by human microvascular endothelial cells when cultured in the presence of varying concentrations of dHACM extract. Endothelial cells increased production of a number of angiogenic factors when cultured in the presence of dHACM extract, compared to untreated cells cultured without extract (green/blue). A few regulatory factors were also down regulated in the presence of extract (red/yellow), while many factors remained unchanged (black), relative to untreated controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4016655&req=5

Figure 2: Change in growth factor production by human microvascular endothelial cells when cultured in the presence of varying concentrations of dHACM extract. Endothelial cells increased production of a number of angiogenic factors when cultured in the presence of dHACM extract, compared to untreated cells cultured without extract (green/blue). A few regulatory factors were also down regulated in the presence of extract (red/yellow), while many factors remained unchanged (black), relative to untreated controls.
Mentions: The induction of specific growth factor production by endothelial cells in culture caused by extracts of dHACM is shown in Figure 2. HMVECs greatly increased production of a number of angiogenic factors including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, TGF-β3, HB-EGF, and interleukin-2 (IL-2) when cultured in the presence of dHACM extract, compared to untreated cells cultured without extract (Figure 2, green). HMVECs also increased production of molecules such as IL-6, angiogenin, and PDGF-BB to a lesser degree in the presence of extract (Figure 2, blue). A few regulatory factors including tumor necrosis factor α (TNF-α) and IL-10 were down regulated in the presence of extract (Figure 2, red/yellow), while many factors such as bFGF, HGF, and TGF-β1 remained unchanged (black), relative to untreated controls.

Bottom Line: Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro.Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process.TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

View Article: PubMed Central - HTML - PubMed

Affiliation: MiMedx Group, Inc., 1775 West Oak Commons Ct., Marietta, GA, USA.

ABSTRACT

Background: Chronic wounds are associated with a number of deficiencies in critical wound healing processes, including growth factor signaling and neovascularization. Human-derived placental tissues are rich in regenerative cytokines and have been shown in randomized clinical trials to be effective for healing chronic wounds. In this study, PURION® Processed (MiMedx Group, Marietta, GA) dehydrated human amnion/chorion membrane tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for properties to support wound angiogenesis.

Methods: Angiogenic growth factors were identified in dHACM tissues using enzyme-linked immunosorbent assays (ELISAs), and the effects of dHACM extract on human microvascular endothelial cell (HMVEC) proliferation and production of angiogenic growth factors was determined in vitro. Chemotactic migration of human umbilical vein endothelial cells (HUVECs) toward pieces of dHACM tissue was determined using a standard in vitro transwell assay. Neovascularization of dHACM in vivo was determined utilizing a murine subcutaneous implant model.

Results: Quantifiable levels of the angiogenic cytokines angiogenin, angiopoietin-2 (ANG-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), platelet derived growth factor BB (PDGF-BB), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were measured in dHACM. Soluble cues promoted HMVEC proliferation in vitro and increased endogenous production of over 30 angiogenic factors by HMVECs, including granulocyte macrophage colony-stimulating factor (GM-CSF), angiogenin, transforming growth factor β3 (TGF-β3), and HB-EGF. 6.0 mm disks of dHACM tissue were also found to recruit migration of HUVECs in vitro. Moreover, subcutaneous dHACM implants displayed a steady increase in microvessels over a period of 4 weeks, indicative of a dynamic intra-implant neovascular process.

Conclusions: TAKEN TOGETHER, THESE RESULTS DEMONSTRATE THAT DHACM GRAFTS: 1) contain angiogenic growth factors retaining biological activity; 2) promote amplification of angiogenic cues by inducing endothelial cell proliferation and migration and by upregulating production of endogenous angiogenic growth factors by endothelial cells; and 3) support the formation of blood vessels in vivo. dHACM grafts are a promising wound care therapy with the potential to promote revascularization and tissue healing within poorly vascularized, non-healing wounds.

No MeSH data available.


Related in: MedlinePlus