Lymphangiogenesis in tissue-engineered small intestine.
BACKGROUND
Lymphangiogenesis, the formation of lymphatic vessels, has not been reported in engineered tissue. The purpose of this study was to characterize lymphangiogenesis in tissue-engineered small intestine.


METHODS
Biodegradable polymer scaffolds seeded with intestinal organoid units were implanted into syngenic recipient rats. Twenty-three neointestinal grafts were harvested from adult rat recipients 1 to 8 weeks postimplantation. Cells expressing the lymphatic endothelial marker vascular endothelial growth factor receptor (VEGFR)-3 were detected immunohistochemically. The lymphangiogenic growth factor VEGF-C was quantified by enzyme-linked immunoadsorbent assay.


RESULTS
Between the first and eighth weeks, neointestinal cysts increased in volume and mass. Muscular and mucosal layers increased in thickness and developed to resemble normal intestine histologically. The proportion of neointestinal VEGFR-3-positive cells increased and ultimately, tubular structures developed that resembled lymphatics architecturally, were distinct from CD34-positive blood vessels, and lacked luminal erythrocytes.


CONCLUSIONS
Lymphangiogenesis occurs in tissue-engineered small intestine. This is the first demonstration of lymphatic vessels in an engineered tissue.
Duxbury
Mark S
MS
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Grikscheit
Tracy C
TC
Gardner-Thorpe
James
J
Rocha
Flavio G
FG
Ito
Hiromichi
H
Perez
Alexander
A
Ashley
Stanley W
SW
Vacanti
Joseph P
JP
Whang
Edward E
EE
D000818:Animals; D007421:Intestine, Small / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism / Q000637:transplantation*; D042583:Lymphangiogenesis; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D023822:Tissue Engineering; D014185:Transplantation, Isogeneic; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
D040321:Vascular Endothelial Growth Factor Receptor-3