title: A study of a three-dimensional PLGA sponge containing natural polymers co-cultured with endothelial and mesenchymal stem cells as a tissue engineering scaffold.
abstract: The interaction between vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in a complex hemodynamic and mechanical environment plays an important role in the control of blood vessel growth and function. Despite the importance of VSMCs, substitutes are needed for vascular therapies. A potential VSMC substitute is human adult bone marrow derived mesenchymal stem cells (hMSCs). In this study, the effect of poly(lactic-co-glycolic acid) (PLGA) scaffolds containing three natural polymers (demineralized bone particles, silk, and small intestine submucosa) on the phenotype of MSCs and SMCs cultured with or without ECs was investigated. The study objective was to create a media equivalent for a tissue engineered blood vessel using PLGA, natural polymers, and MSCs co-cultured with ECs. The PLGA containing the natural polymers silk and SIS showed increased proliferation and cell adhesion. The presence of silk and DBP promoted a MSC phenotype change into a SMC-like phenotype at the mRNA level; however these differences at the protein level were not seen. Additionally, PLGA containing SIS did not induce SMC gene or protein upregulation. Finally, the effect of ECs in combination with the natural polymers was tested. When co-cultured with ECs, the mRNA of SMC specific markers in MSCs and SMCs were increased when compared to SMCs or MSCs alone. However, MSCs, when co-cultured with ECs on PLGA containing silk, exhibited significantly increased α-SMA and calponin expression when compared to PLGA only scaffolds. These results indicate that the natural polymer silk in combination with the co-culture of endothelial cells was most effective at increasing cell viability and inducing a SMC-like phenotype at the mRNA and protein level in MSCs.
authors: Department of BIN Fusion Technology & Polymer Fusion Research Center, Chonbuk National University, Jeonju, Republic of Korea.
authors: Jung Bo
authors: JB
authors: Shim
authors: Randall F
authors: RF
authors: Ankeny
authors: Hyeongseok
authors: H
authors: Kim
authors: Robert M
authors: RM
authors: Nerem
authors: Gilson
authors: G
authors: Khang
mesh_terms: D001011:Aorta / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry; D001854:Bone Marrow Cells / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002470:Cell Survival; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology; D006439:Hemodynamics; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008840:Microfilament Proteins / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010641:Phenotype; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D000096985:Calponins
chemical_list: D001672:Biocompatible Materials; D002135:Calcium-Binding Proteins; D019344:Lactic Acid; D008840:Microfilament Proteins; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000096985:Calponins