Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

Garcia, Briana M.; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; Paepe, Monique E. De; Gruppuso, Philip A.; Sanders, Jennifer

doi:10.1194/jlr.d052787

Cited by 2 publications

(7 citation statements)

References 27 publications

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“…Renal subcapsular xenotransplants in comparison to subcutaneous xenotransplants have superior access to the host vasculature (Wang et al, 2005). In our studies, human fetal testis, lung, adipose tissue, and prostate xenotransplants maintain donor tissue-derived vascularization, as evidenced by immunohistochemical localization of the human endothelial marker CD31 (De Paepe et al, 2012a;Heger et al, 2012;Saffarini et al, 2013;Garcia et al, 2014;Fig. 2).…”

Section: Xenotransplantation Proceduresmentioning

confidence: 64%

“…). In fetal lung and adipose tissue, we have further demonstrated that human CD31‐positive blood vessels extend from the xenotransplant into the renal cortex of the host (De Paepe et al., ; Garcia et al., ; Fig. ).…”

Section: Considerations For Development Of Xenotransplantation Modelsmentioning

confidence: 88%

“…However, small foci of developing adipose tissue were apparent by 2 weeks. Obvious fat pads were present at 4 weeks and beyond (Garcia et al., ). Histologic analysis of the fat pads showed evidence of adipogenesis (marked variability in adipocyte size) and maintenance of healthy adipocytes.…”

Section: Human Fetal Tissue Xenotransplant Models To Study the Mechanmentioning

confidence: 99%

“…In this review, we describe our recent development of xenotransplant models with the goal of studying the effects of xenobiotics in human fetal testis (Heger et al., ; Spade et al., ), prostate (Saffarini et al., ), lung (De Paepe et al., , ), liver, and adipose tissue (Garcia et al., ). We do not aim to conduct an exhaustive review of the extensive literature on xenotransplantation.…”

Section: Introductionmentioning

confidence: 99%

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Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues

Spade

McDonnell

Heger

et al. 2014

Birth Defects Research Pt B

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Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development.

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Section: Xenotransplantation Proceduresmentioning

confidence: 64%

Section: Considerations For Development Of Xenotransplantation Modelsmentioning

confidence: 88%

Section: Human Fetal Tissue Xenotransplant Models To Study the Mechanmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues

Spade

McDonnell

Heger

et al. 2014

Birth Defects Research Pt B

Self Cite

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“…Transplantation of pancreatic β‐cells, thermogenic, fetal and genetically modified adipocytes, and other minor cell populations showed therapeutic promise for treatment of many degenerative disorders including diabetes and obesity. However, systemic and immune effects in vivo limit possibilities to dissect mechanisms for interaction between xenograft and host organism.…”

Section: Discussionmentioning

confidence: 99%

Aldehyde dehydrogenase 1 a1 regulates energy metabolism in adipocytes from different species

Yang

Adin

Shen

et al. 2017

Xenotransplantation

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Background Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for inter-species crosstalk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes. Deficient retinoic acid production in aldehyde dehydrogenase 1 family fember A1 (Aldh1a1) knock out adipocytes (KO) inhibits adipogenesis and increase thermogenesis. Here we test the role Aldh1a1 in regulation of lipid metabolism in xenocultures. Methods Murine wide type (WT) and KO preadipocytes were encapsulated into a poly-L-lysine polymer that allows exchange of humoral factors <32kD via nanopores. Encapsulated murine adipocytes were co-incubated with primary differentiated canine adipocytes. Then, expression of adipogenic and thermogenic genes in differentiated canine adipocytes were detected by real-time polymerase chain reaction (PCR). The regulatory factors in WT and KO cells were identified by comparison of secretome using proteomics and in transcriptome by gene microarray. Results Co-culture of encapsulated mouse KO vs. WT adipocytes increased expression of peroxisome proliferator-activated receptor gamma (Pparg), but reduced expression of its target genes fatty acid binding protein 4 (Fabp4), and adipose triglyceride lipase (Atgl) in canine adipocytes, suggesting inhibition of PPARγ activation. Co-culture with KO adipocytes also induced expression of Ucp1 in canine adipocytes compared to expression with WT adipocytes. Cumulatively, murine KO compared to WT adipocytes decreased lipid accumulation in canine adipocytes. Comparative proteomics revealed significantly higher levels of vitamin A carriers, retinol binding protein 4 (RBP4) and lipokalin 2 (LCN2) in KO vs WT adipocytes. Conclusion Our data demonstrate the functional exchange of regulatory factors between adipocytes from different species for regulation of energy balance. RBP4 and LCN2 appear to be involved in the transport of retinoids for regulation of lipid accumulation and thermogenesis in xenocultures. While the rarity of thermogenic adipocytes in humans and dogs precludes their use for autologous transplantation, our study demonstrates that xenotransplantation of engineered cells could be a potential solution for reduction of obesity in dogs and a strategy for translation to patients.

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Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

Cited by 2 publications

References 27 publications

Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues

Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues

Aldehyde dehydrogenase 1 a1 regulates energy metabolism in adipocytes from different species

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