Normal and glucocorticoid-induced development of the human small intestinal xenograft.
The aim of this study was to determine whether intestinal xenografts could recapitulate human in utero development by using disaccharidases as markers. Twenty-week-old fetal intestine was transplanted into immunocompromised mice and was followed. At 20-wk of gestation, the fetal human intestine was morphologically developed with high sucrase and trehalase but had low lactase activities. By 9-wk posttransplantation, jejunal xenografts were morphologically and functionally developed and were then monitored for </=6 mo. Both sucrase and trehalase activities remained unchanged, but lactase activity increased in a manner similar to that described in in utero development. Changes in sucrase and lactase activities were paralleled by protein levels. Cortisone acetate treatment at 20-wk posttransplantation accelerated the ontogeny of lactase but did not alter sucrase and trehalase activities. Biopsies from 1- and 2-yr-old infant intestine showed that all activities, except trehalase in the proximal intestine, corresponded to the levels found in jejunal xenografts at 24 wk posttransplantation. These studies suggest that 20-wk-old fetal intestine has the extrauterine developmental potential to follow normal intrauterine ontogeny as a xenograft.
Nanthakumar
N Nanda
NN
Developmental Gastroenterology Laboratory, Massachusetts General Hospital-East, 114 16th St.: Rm. 3650, Charlestown, MA 02129, USA. nanthaku@helix.mgh.harvard.edu
Klopcic
Corrie E
CE
Fernandez
Isabel
I
Walker
W Allan
WA
D000818:Animals; D015415:Biomarkers; D003348:Cortisone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016332:Fetal Tissue Transplantation; D006801:Humans; D007583:Jejunum / Q000201:enzymology / Q000254:growth & development / Q000637:transplantation*; D043322:Lactase; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D013393:Sucrase / Q000378:metabolism; D014183:Transplantation, Heterologous; D014198:Trehalase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D015415:Biomarkers; D043322:Lactase; D001616:beta-Galactosidase; D014198:Trehalase; D013393:Sucrase; D003348:Cortisone