title: Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis.
abstract: Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology.
authors.affiliation: Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, Providence, RI 02903.
authors.forename: Briana
authors.initials: B
authors.lastname: Garcia
authors.affiliation: Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, Providence, RI 02903.
authors.forename: Heather
authors.initials: H
authors.lastname: Francois-Vaughan
authors.affiliation: Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, Providence, RI 02903.
authors.forename: Omobola
authors.initials: O
authors.lastname: Onikoyi
authors.affiliation: Department of Pathology and Laboratory Medicine, Women and Infants Hospital and Brown University, Providence, RI 02903.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kostadinov
authors.affiliation: Department of Pathology and Laboratory Medicine, Women and Infants Hospital and Brown University, Providence, RI 02903.
authors.forename: Monique E
authors.initials: ME
authors.lastname: De Paepe
authors.affiliation: Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, Providence, RI 02903.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Gruppuso
authors.affiliation: Division of Pediatric Endocrinology, Rhode Island Hospital and Brown University, Providence, RI 02903.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Sanders
mesh_terms: D000028:Abortion, Induced; D050156:Adipogenesis; D000328:Adult; D000818:Animals; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006801:Humans; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D007668:Kidney; D008297:Male; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D050497:Stillbirth; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
keywords: adipocytes; angiogenesis; nutrition; obesity; pregnancy