Engineering functional blood vessels in vivo

At the present time, there are many hurdles to overcome in order to create a long-lasting and engineered tissue for tissue transplant in patients. The challenges include the isolation and expansion of appropriate cells, the arrangement of assorted cells into correct spatial organization, and the development of proper growth conditions. Furthermore, the creation of a three dimensional engineered tissue is limited by the fact that tissue assemblies greater than 100-200 micrometers, the limit of oxygen diffusion, require a perfused vascular bed to supply nutrients and to remove waste products and metabolic intermediates. To overcome this limitation, this thesis aims to pre-seed a tissue engineered construct with vascular cells (both endothelial and perivascular cells), so the vascular cells could readily form functional vessels in situ. Previous work in the laboratory had successfully demonstrated the formation of functional microvascular network by co-implantation of human umbilical cord vein endothelial cells (HUVECs) and 10 T 1/2 cells, a line of mouse embryonic fibroblasts. To translate this concept to the clinic, we need to utilize cells that can be secured and used in clinic. To this end, we systematically replace each individual vascular cell type with a readily available source of cells. First, we investigated human embryonic stem cells (hESCs) derived endothelial cells. We demonstrated that when hESCs derived endothelial cells were implanted into SCID mice, they formed blood vessels that integrated into the host circulatory system and served as blood conduits. Second, we compared the formation and function of engineered blood vessels generated from circulating endothelial progenitor cells (EPCs) derived from either adult peripheral blood or umbilical cord blood.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Au, Pakwai

Advisor dc:contributor.advisor

• Rakesh K. Jain.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/43867

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/43867