title: In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid-derived stem cells.
abstract: One of the greatest challenges in regenerative medicine is generating clinically relevant engineered tissues with functional blood vessels. Vascularization is a key hurdle faced in designing tissue constructs larger than the in vivo limit of oxygen diffusion. In this study, we utilized fibrin-based hydrogels to serve as a foundation for vascular formation, poly(ethylene glycol) (PEG) to modify fibrinogen and increase scaffold longevity, and human amniotic fluid-derived stem cells (AFSC) as a source of vascular cell types (AFSC-EC). AFSC hold great potential for use in regenerative medicine strategies, especially those involving autologous congenital applications, and we have shown previously that AFSC-seeded fibrin-PEG hydrogels have the potential to form three-dimensional vascular-like networks in vitro. We hypothesized that subcutaneously injecting these hydrogels in immunodeficient mice would both induce a fibrin-driven angiogenic host response and promote in situ AFSC-derived neovascularization. Two weeks postinjection, hydrogels were sectioned, and the following was demonstrated: the average maximum invasion distance of host murine cells into the subcutaneous fibrin/PEG scaffold was 147 ± 90 µm after 1 week and 395 ± 138 µm after 2 weeks; the average number of cell-lined lumen per square millimeter was significantly higher in hydrogels seeded with stem cells or cocultures containing stem cells (MSC, 36.5 ± 11.4; AFSC, 47.0 ± 18.9; AFSC/AFSC-EC, 32.8 ± 11.6; and MSC/HUVEC, 43.1 ± 25.1) versus endothelial cell types alone (AFSC-EC, 9.7 ± 6.1; HUVEC, 14.2 ± 8.8); and a subset of these lumen were characterized by the presence of red blood cells. Select areas of cell-seeded hydrogels contained CD31(+) lumen surrounded by α-smooth muscle cell support cells, whereas control hydrogels with no cells only showed infiltration of α-smooth muscle cell-positive host cells.
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Omar M
authors: OM
authors: Benavides
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Abigail R
authors: AR
authors: Brooks
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Sung Kyung
authors: SK
authors: Cho
authors: Department of Bioengineering, Rice University, Houston, Texas.
authors: Jennifer
authors: J
authors: Petsche Connell
authors: Maternal-Fetal Medicine, Baylor College of Medicine, Houston, Texas.
authors: Rodrigo
authors: R
authors: Ruano
authors: Department of Bioengineering, Rice University, Houston, Texas.|Congenital Heart Surgery Services, Texas Children's Hospital, Houston, Texas.
authors: Jeffrey G
authors: JG
authors: Jacot
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005337:Fibrin; D006801:Humans; D020100:Hydrogels; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols; D013234:Stem Cells / Q000166:cytology*
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols; D005337:Fibrin
keywords: amniotic fluid-derived stem cells; angiogenesis; fibrin; hydrogels; vasculogenesis