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Current advances in the translation of vascular tissue engineering to the treatment of pediatric congenital heart disease.

Dean EW, Udelsman B, Breuer CK - Yale J Biol Med (2012)

Bottom Line: Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies.Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential.The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Program in Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, CT 06520, USA.

ABSTRACT
Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies. Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential. The first pilot clinical trial of TEVGs demonstrated the feasibility of this new technology and revealed an excellent safety profile. However, long-term follow-up from this trial revealed the primary graft-related complication to be stenosis, affecting 16 percent of grafts within 7 years post-implantation. In order to determine the mechanism behind TEVG stenosis and ultimately to create improved second generation TEVGs, our group has returned to the bench to study vascular neotissue formation in a variety of large and small animal models. The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering.

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Related in: MedlinePlus

TEVG development in mouse model. Early pulse of cytokine (MCP-1) release from seeded BM-MNC enhances monocyte recruitment to the scaffold. Monocytes infiltrate the scaffold and direct neotissue formation, leading to the recruitment of smooth muscle cells from neighboring native vessel wall. This process results in concentric layers of smooth muscle cells embedded in an extracellular matric with a monolayer of endothelial cells lining the luminal surface. (Adapted with permission from Roh (2010) [41]).
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Figure 2: TEVG development in mouse model. Early pulse of cytokine (MCP-1) release from seeded BM-MNC enhances monocyte recruitment to the scaffold. Monocytes infiltrate the scaffold and direct neotissue formation, leading to the recruitment of smooth muscle cells from neighboring native vessel wall. This process results in concentric layers of smooth muscle cells embedded in an extracellular matric with a monolayer of endothelial cells lining the luminal surface. (Adapted with permission from Roh (2010) [41]).

Mentions: Extensive histological and immunohistochemical characterization was performed to investigate the mechanism by which neotissue formation within the TEVGs occurred. Although it has been hypothesized that stem cells within the seeded BM-MNC population differentiate into the cells of the neotissue [42], by 1 week after implantation, human BM-MNCs were no longer detectable within the TEVGs. Rather, it is hypothesized that these seeded cells augment a host inflammatory process via a paracrine mechanism through the secretion of chemokines that recruit host cells to the scaffold, ultimately leading to neovascularization. When compared to unseeded grafts, seeded grafts demonstrated a higher concentration of macrophages during early graft development. Notably, interleukin 1-beta (IL-1B) and monocyte chemoattractant protein-1 (MCP-1) were both found in abundant quantity. Later experiments utilized alginate microspheres containing MCP-1. Implanted TEVGs with alginate microspheres incorporated into their walls developed and functioned similar to human BM-MNC-seeded scaffolds with an internal lumen containing organized vascular neotissue [41] (Figure 2).


Current advances in the translation of vascular tissue engineering to the treatment of pediatric congenital heart disease.

Dean EW, Udelsman B, Breuer CK - Yale J Biol Med (2012)

TEVG development in mouse model. Early pulse of cytokine (MCP-1) release from seeded BM-MNC enhances monocyte recruitment to the scaffold. Monocytes infiltrate the scaffold and direct neotissue formation, leading to the recruitment of smooth muscle cells from neighboring native vessel wall. This process results in concentric layers of smooth muscle cells embedded in an extracellular matric with a monolayer of endothelial cells lining the luminal surface. (Adapted with permission from Roh (2010) [41]).
© Copyright Policy - open access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375656&req=5

Figure 2: TEVG development in mouse model. Early pulse of cytokine (MCP-1) release from seeded BM-MNC enhances monocyte recruitment to the scaffold. Monocytes infiltrate the scaffold and direct neotissue formation, leading to the recruitment of smooth muscle cells from neighboring native vessel wall. This process results in concentric layers of smooth muscle cells embedded in an extracellular matric with a monolayer of endothelial cells lining the luminal surface. (Adapted with permission from Roh (2010) [41]).
Mentions: Extensive histological and immunohistochemical characterization was performed to investigate the mechanism by which neotissue formation within the TEVGs occurred. Although it has been hypothesized that stem cells within the seeded BM-MNC population differentiate into the cells of the neotissue [42], by 1 week after implantation, human BM-MNCs were no longer detectable within the TEVGs. Rather, it is hypothesized that these seeded cells augment a host inflammatory process via a paracrine mechanism through the secretion of chemokines that recruit host cells to the scaffold, ultimately leading to neovascularization. When compared to unseeded grafts, seeded grafts demonstrated a higher concentration of macrophages during early graft development. Notably, interleukin 1-beta (IL-1B) and monocyte chemoattractant protein-1 (MCP-1) were both found in abundant quantity. Later experiments utilized alginate microspheres containing MCP-1. Implanted TEVGs with alginate microspheres incorporated into their walls developed and functioned similar to human BM-MNC-seeded scaffolds with an internal lumen containing organized vascular neotissue [41] (Figure 2).

Bottom Line: Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies.Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential.The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Program in Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, CT 06520, USA.

ABSTRACT
Tissue-engineered vascular grafts (TEVGs) hold great promise for the improvement of outcomes in pediatric patients with congenital cardiac anomalies. Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential. The first pilot clinical trial of TEVGs demonstrated the feasibility of this new technology and revealed an excellent safety profile. However, long-term follow-up from this trial revealed the primary graft-related complication to be stenosis, affecting 16 percent of grafts within 7 years post-implantation. In order to determine the mechanism behind TEVG stenosis and ultimately to create improved second generation TEVGs, our group has returned to the bench to study vascular neotissue formation in a variety of large and small animal models. The purpose of this report is to review the recent advances in the understanding of neotissue formation and vascular tissue engineering.

Show MeSH
Related in: MedlinePlus