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

Vascular Cell

William W Li²  Geoffrey Gurtner¹  Robert Rennert¹  Nicole Zabek³  Michelle Massee³  Jeremy J Lim³  Thomas J Koob³ 

[1] Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA;The Angiogenesis Foundation, Cambridge, MA, USA;MiMedx Group, Inc., 1775 West Oak Commons Ct., Marietta, GA, USA

关键词: Chronic wounds;    Wound healing;    Soft tissue regeneration;    Endothelial cells;    VEGF;    Growth factors;    Angiogenesis;    dHACM;    Amnion/chorion grafts;    Chorion;    Amnion;   

Others  :  801193
DOI  :  10.1186/2045-824X-6-10

 received in 2013-11-20, accepted in 2014-03-26,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Koob et al.; licensee BioMed Central Ltd.

【 图 表 】

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