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Regen Med. 2011 Sep;6(5):559-67. doi: 10.2217/rme.11.49.

VEGF optimizes the formation of tissue-engineered small intestine.

Author information

1
Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children's Hospital Los Angeles, 4650 W Sunset Blvd, MS#100, Los Angeles, CA 90027, USA.

Abstract

AIM:

To determine the effect of VEGF overexpression on tissue-engineered small intestine (TESI) formation.

MATERIALS & METHODS:

Organoid units were isolated from the intestines of 2-week-old transgenic mouse pups capable of inducible, ubiquitous VEGF overexpression (CMV-Cre/rtTA/tet(0)-VEGF) and implanted into nonobese diabetic/severe combined immunodeficiency mice. Resulting TESI were explanted at 2 and 4 weeks, and studied by histology, tissue ELISA and immunofluorescence.

RESULTS:

At 2 weeks postimplantation, the TESI mucosa from the VEGF overexpression group formed rudimentary villi and more crypts compared with controls, which demonstrated a flat epithelium with few crypts and no villi. At 4 weeks postimplantation, the TESI from the VEGF overexpression group was larger and significantly heavier than controls. Within the mucosa, the villus height and crypt depth was significantly longer, contained a greater percentage of proliferating crypt epithelial cells and consisted of all four terminally differentiated epithelial cell types. There was also a significant increase in the capillary density within the submucosa.

CONCLUSIONS:

Overexpression of VEGF optimizes the formation of TESI by increasing the submucosal capillary density, crypt epithelial proliferation and the rate of mucosa formation. A larger construct with increased villus and crypt height was noted after 4 weeks in vivo.

PMID:
21916592
DOI:
10.2217/rme.11.49
[Indexed for MEDLINE]

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