Developmental Regulation of Intestinal Epithelial Hydrolase Activity in Human Fetal Jejunal Xenografts Maintained in Severe-Combined Immunodeficient Mice

Savidge, Tor; Lowe, David C.; Walker, W. Allan

doi:10.1203/00006450-200108000-00006

Cited by 17 publications

(15 citation statements)

References 36 publications

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“…In these studies, we have used 20-wk-old fetal tissues for xenotransplantation, whereas other studies (36,37,48) have used 10-to 14-wk-old fetal tissue. Thus it was not clear whether 20-wk-old tissues were capable of regenerating as a xenograft.…”

Section: Discussionmentioning

confidence: 99%

“…Sterile fetal small intestine in 2-cm segments stripped of its mesentery was implanted subcutaneously into homozygous nude or scid mice as described previously (36,37,48). Clear and meconium-free jejunal tissues were used for xenotransplantation, because tissue could be easily obtained with minimal handling before surgery.…”

Section: Methodsmentioning

confidence: 99%

“…A lack of availability of human tissue has precluded testing of this hypothesis as well as identifying other markers for the late gestational development of the fetal human intestine. However, the recent demon-stration of disaccharidase expression in the xenograft model (36) has provided an opportunity to test this hypothesis.…”

mentioning

confidence: 99%

“…With the establishment of a xenograft model, fetal human gut subcutaneously transplanted into immunocompromised mice has the capability of regenerating and surviving in these hosts for extended periods of time (36,37,48). However, there has been a lack of systematic evaluation of xenografts as a function of time posttransplant to determine whether this model could be used to study the ontogeny of the human intestine in the later stages of gestation.…”

mentioning

confidence: 99%

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Normal and glucocorticoid-induced development of the human small intestinal xenograft

Nanthakumar

Klopcic

Fernández

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Normal and glucocorticoid-induced development of the human small intestinal xenograft

Nanthakumar

Klopcic

Fernández

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…For example, ectopic grafting of fetal jejunum closely recapitulated the development of these enzymes in utero, with alkaline phosphatase, aminopeptidase-N, ␣-glucosidase, and dipeptidyl peptidase IV enzyme activities closely matching the spatiotemporal distribution and levels recorded in pediatric duodenal biopsies (24). Lactase-phlorizin hydrolase activity was the only enzyme that failed to reach pediatric values, although activities were comparable to late-gestational-age human fetal bowel.…”

Section: Discussionmentioning

confidence: 79%