The Xenotransplantation Core provides specialized, on-demand surgical services for the transplantation and evaluation of human fetal tissues in immunodeficient animals in support of the research projects carried out by the Formative Center. The core is responsible for the coordination of immunodeficient animal procurement (nude rats) with anticipated availability of fetal tissues, and sterile renal subcapsular or subcutaneous transplantation of appropriate fetal source tissue upon availability. Our group has demonstrated that fetal testis, handled and processed in the usual manner by hospital staff, is histopathologically responsive to selective toxicant exposure when implanted under the kidney capsule of nude rats. The Xenotransplantation Core facilitates the expansion of this past work into other fetal tissue types and environmental impacts by centralizing development of the xenografted animal model in support of the three primary research areas of the Formative Center: Metabolic Syndrome. Prostate Imprinting, and Lung Remodeling. The Xenotransplantation Core will function as the site of the initiation of the experiments carried out in the Formative Center's Research Projects by providing an on-demand service that coordinates with the Tissue Procurement Core to transplant fetal tissue as it becomes available into xenogeneic hosts. As such, the Core will maintain host animals for instant availability, and its personnel will have the shared responsibility of performing surgical requests within a time frame that allows confidence in graft viability upon implantation. The Xenotransplantation Core will pursue these Specific Aims: ? Specific Aim 1 - Provide animal surgery and model development services ? Specific Aim 2 - Interact with research investigators to initiate animal experiments in support of the Formative Center's research projects ? Specific Aim 3 - Implement current and emerging surgical techniques in xenotransplant model development and training of technical staff

Public Health Relevance

The overarching goal of this Formative Center is to develop novel biomarkers for the adverse effects of environmental exposures that impact fetal development and produce childhood and adult disease. Using an interdisciplinary approach, research, educational, and training interventions will be designed to address the concerns that pregnant women, families, and communities have about environmental chemicals and the health of their developing children.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZES1)
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Brown University
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Saffarini, Camelia M; McDonnell-Clark, Elizabeth V; Amin, Ali et al. (2015) Developmental exposure to estrogen alters differentiation and epigenetic programming in a human fetal prostate xenograft model. PLoS One 10:e0122290
Huse, Susan M; Gruppuso, Philip A; Boekelheide, Kim et al. (2015) Patterns of gene expression and DNA methylation in human fetal and adult liver. BMC Genomics 16:981
De Paepe, Monique E; Chu, Sharon; Hall, Susan J et al. (2015) Intussusceptive-like angiogenesis in human fetal lung xenografts: Link with bronchopulmonary dysplasia-associated microvascular dysangiogenesis? Exp Lung Res 41:477-88
Saffarini, Camelia M; McDonnell-Clark, Elizabeth V; Amin, Ali et al. (2015) A human fetal prostate xenograft model of developmental estrogenization. Int J Toxicol 34:119-28
Spade, Daniel J; McDonnell, Elizabeth V; Heger, Nicholas E et al. (2014) Xenotransplantation models to study the effects of toxicants on human fetal tissues. Birth Defects Res B Dev Reprod Toxicol 101:410-22
Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola et al. (2014) Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis. J Lipid Res 55:2685-91
Saffarini, Camelia M; McDonnell, Elizabeth V; Amin, Ali et al. (2013) Maturation of the developing human fetal prostate in a rodent xenograft model. Prostate 73:1761-75
De Paepe, Monique E; Chu, Sharon; Heger, Nicholas et al. (2012) Resilience of the human fetal lung following stillbirth: potential relevance for pulmonary regenerative medicine. Exp Lung Res 38:43-54
Campion, Sarah; Catlin, Natasha; Heger, Nicholas et al. (2012) Male reprotoxicity and endocrine disruption. EXS 101:315-60
Panikkar, Bindu; Smith, Natasha; Brown, Phil (2012) Reflexive research ethics in fetal tissue xenotransplantation research. Account Res 19:344-69

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