1 of the major obstacles in tissue engineering of thick, complex tissues (such as the heart and the liver) is the need to vascularize the tissue in vitro. Vascularization in vitro could restore cells viability during growth of the tissue, induce structural organization and promote integration upon implantation. Embryonic stem (ES) cells have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. We have shown that human ES (hES) cells can differentiate into endothelial cells (ECs) forming vascular-like structures when formation of embryoid bodies is induced and that these cells can be isolated and grown in culture. We hypothesize that the vasculogenic potential of hES-derived endothelial progenitors can be used to induce vascularization in engineered human tissue. Our goal will be to induce vasculogenesis in engineered tissue constructs grown on three dimensional (3D) polymer scaffolds. We will use co culture systems of embryonic endothelial and cardiac cells cultured on biodegradable polymer scaffolds designed to meet cellular and mechanical properties needed for a cardiac patch. The vascularized constructs will be implanted and examined for integration with the host vasculature. We hypothesize that the vessel network created in vitro will promote the vascularization of the tissue in vivo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL060435-06A2
Application #
6921180
Study Section
Special Emphasis Panel (ZRG1-CDD (01))
Program Officer
Lundberg, Martha
Project Start
1998-07-10
Project End
2009-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
6
Fiscal Year
2005
Total Cost
$350,820
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Langer, Robert; Vacanti, Joseph (2016) Advances in tissue engineering. J Pediatr Surg 51:8-12
Saigal, Rajiv; Cimetta, Elisa; Tandon, Nina et al. (2013) Electrical stimulation via a biocompatible conductive polymer directs retinal progenitor cell differentiation. Conf Proc IEEE Eng Med Biol Soc 2013:1627-31
Kraehenbuehl, Thomas P; Ferreira, Lino S; Hayward, Alison M et al. (2011) Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction. Biomaterials 32:1102-9
Ghosh, Fredrik; Neeley, William L; Arnér, Karin et al. (2011) Selective removal of photoreceptor cells in vivo using the biodegradable elastomer poly(glycerol sebacate). Tissue Eng Part A 17:1675-82
Zoldan, Janet; Karagiannis, Emmanouil D; Lee, Christopher Y et al. (2011) The influence of scaffold elasticity on germ layer specification of human embryonic stem cells. Biomaterials 32:9612-21
Kraehenbuehl, Thomas P; Langer, Robert; Ferreira, Lino S (2011) Three-dimensional biomaterials for the study of human pluripotent stem cells. Nat Methods 8:731-6
Levenberg, Shulamit; Ferreira, Lino S; Chen-Konak, Limor et al. (2010) Isolation, differentiation and characterization of vascular cells derived from human embryonic stem cells. Nat Protoc 5:1115-26
Pritchard, Christopher D; Arnér, Karin M; Langer, Robert S et al. (2010) Retinal transplantation using surface modified poly(glycerol-co-sebacic acid) membranes. Biomaterials 31:7978-84
Pritchard, Christopher D; Arnér, Karin M; Neal, Rebekah A et al. (2010) The use of surface modified poly(glycerol-co-sebacic acid) in retinal transplantation. Biomaterials 31:2153-62
Fisher, Omar Z; Khademhosseini, Ali; Langer, Robert et al. (2010) Bioinspired materials for controlling stem cell fate. Acc Chem Res 43:419-28

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