Xenografted Human Whole Embryonic and Fetal Entoblastic Organs Develop and Become Functional Adult-like Micro-organs

Angioï, K.; Hatier, R; Merle, M.; Duprez, A

doi:10.1006/jsre.2001.6293

Cited by 11 publications

(4 citation statements)

References 21 publications

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“…Among them are such widespread diseases as diabetes, end-stage renal disease, Parkinson's disease, acute and chronic liver failure, and inherited metabolic disorders. The efficacy of committed embryonic pig or human kidney (13,28), pancreas (29)(30)(31)(32)(33)(34), lung (35), heart, or intestine (35,36) as well as hepatocytes (37)(38)(39)(40) or neuronal precursors (41)(42)(43), which grew and differentiated upon implantation into SCID or nude mice or rats, has been extensively Embryonic pig pancreas tissues obtained at various gestational ages were implanted under the kidney capsule. Tissue growth and serum levels of pig insulin were evaluated 6 weeks after implantation as described in Methods.…”

Section: Discussionmentioning

confidence: 99%

Embryonic pig liver, pancreas, and lung as a source for transplantation: Optimal organogenesis without teratoma depends on distinct time windows

Eventov‐Friedman

Katchman

Shezen

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Pig embryonic tissues represent an attractive option for organ transplantation. However, the achievement of optimal organogenesis after transplantation, namely, maximal organ growth and function without teratoma development, represents a major challenge. In this study, we determined distinct gestational time windows for the growth of pig embryonic liver, pancreas, and lung precursors. Transplantation of embryonic-tissue precursors at various gestational ages [from E (embryonic day) 21 to E100] revealed a unique pattern of growth and differentiation for each embryonic organ. Maximal liver growth and function were achieved at the earliest teratoma-free gestational age (E28), whereas the growth and functional potential of the pancreas gradually increased toward E42 and E56 followed by a marked decline in insulin-secreting capacity at E80 and E100. Development of mature lung tissue containing essential respiratory system elements was observed at a relatively late gestational age (E56). These findings, showing distinct, optimal gestational time windows for transplantation of embryonic pig liver, pancreas, and lung, might explain, in part, the disappointing results in previous transplantation trials and could help enhance the chances for successful implementation of embryonic pig tissue in the treatment of a wide spectrum of human diseases.fetal ͉ porcine ͉ gestational age ͉ growth potential

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Section: Discussionmentioning

confidence: 99%

Embryonic pig liver, pancreas, and lung as a source for transplantation: Optimal organogenesis without teratoma depends on distinct time windows

Eventov‐Friedman

Katchman

Shezen

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Human intestinal xenografts implanted into the subscapular region of a SCID mouse become vascularized with murine endothelial cells and develop a lumen, with a morphologically precise mucosal layer containing villi and crypts, lamina propria, and muscularis layers [6]. Intestinal xenografts are even capable of nutrient absorption and peristalsis [7]. This model, which closely mimics natural human infection, has now been used to study the interactions between several enteric pathogens and the human intestine.…”

mentioning

confidence: 99%

Mycobacterium avium paratuberculosisInvades Human Small‐Intestinal Goblet Cells and Elicits Inflammation

et al. 2009

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Crohn disease is a chronic inflammatory bowel disease of unknown etiology. Mycobacterium avium paratuberculosis (MAP) was found in the gut of patients with Crohn disease, but causality was not established. Fully developed, germ-free human small intestine and colon were established by subcutaneous transplantation of fetal gut into SCID (severe combined immunodeficiency) mice thereafter infected by direct intraluminal inoculation of MAP. We have found that MAP actively invades the human gut epithelial goblet cells of the small intestine, inducing severe tissue damage and inflammation. These observations indicate that MAP can specifically colonize the normal human small intestine and can elicit inflammation and severe mucosal damage.

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“…In contrast to the other numerous human embryonic fetal organs which we have transplanted into nude mice, and which always develop if the implanting site is well vascularized (Angioi et al . 2001(Angioi et al . , 2002, the eyeball requires a hypervascularized site of transplantation to avoid consistent necrosis of the intraocular tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Using an original method for heterotopic embryonic and fetal organ xenografts into congenitally immunodeficient mice, many fetal organs obtained from legally aborted human fetuses develop normally (Angioi et al . 2001(Angioi et al . , 2002.…”

Section: Introductionmentioning

confidence: 99%

Ocular tissue interactions during the development of human fetal neuroretina grafted into nude mice

Angioï¹,

Hatier

Duprez³

2003

Dev Growth Differ

Self Cite

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To determine the roles of different ocular tissues in the development of the human fetal neuroretina, a study ethically and technically impossible in human subjects, human embryonic and fetal retinas were heterotopically implanted into nude mice. Ninety-five eyeballs were obtained from legally aborted 6- to 7-week-old embryos or 8- to 10-week-old fetuses. Ten isolated neuroretinas with vitreous but without pigment epithelium, 20 half-eyeballs and 70 intact eyeballs, of which 12 had a thick layer of periocular tissue, were microsurgically grafted. Five intact eyeballs were used for reference. Over a period of 1-245 days, all of the grafts were removed for light and electron microscopy observations. All of the isolated neuroretinas had disappeared by the second day after transplantation. Grafts of the posterior section of the eyeball contained only some clusters of pigment epithelium, occasionally covered with undifferentiated neuroretinal cells. Grafts of the retrolental section of the eyeball contained small areas of dysplasic neuroretina with folds and rosettes. Grafts of the 70 intact eyeballs were successful, but only 26 showed normal histological organization of the choriocapillaris, the retinal pigment epithelium and the neuroretina in the posterior part of the posterior chamber. Photoreceptor differentiation was evident in these retinas after approximately 80 days of transplantation and was complete after 166 days. Their anterior part was always dysplasic, with occasional ciliary differentiation. Twenty-three grafted eyeballs had a dysplasic neuroretina with folds, rosettes and necrotized areas. Twenty-one were atrophic, 12 of which were the eyeballs grafted with periocular tissue. These results demonstrate the role of the fetal mesenchyme and pigment epithelium in the rapid revascularization, and subsequent survival and tissue organization, of the neuroretina. The stratified development of the neuroretina required a thin mesenchymal environment for revascularization of the graft by human vasculogenesis or neoangiogenesis and a normal retinal pigment epithelium for normal neuroretinal differentiation. When these conditions were not satisfied, the neuroretina disappeared or was dysplasic, partly necrotized or atrophic. This model might prove useful for a number of therapeutic or clinical studies.

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Xenografted Human Whole Embryonic and Fetal Entoblastic Organs Develop and Become Functional Adult-like Micro-organs

Cited by 11 publications

References 21 publications

Embryonic pig liver, pancreas, and lung as a source for transplantation: Optimal organogenesis without teratoma depends on distinct time windows

Embryonic pig liver, pancreas, and lung as a source for transplantation: Optimal organogenesis without teratoma depends on distinct time windows

Mycobacterium avium paratuberculosisInvades Human Small‐Intestinal Goblet Cells and Elicits Inflammation

Ocular tissue interactions during the development of human fetal neuroretina grafted into nude mice

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