In utero Allotransplantation of Fetal Hepatocytes in Primates

Michelet, Dominique; Loux, Nathalie; Simon, L; Allain, Jean-Etienne; Beaudoın, Sylvie; Bargy, F.; Andreoletti, Marion; Weber, Anne

doi:10.1159/000074269

Cited by 7 publications

(6 citation statements)

References 17 publications

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“…Therefore, maternal immune response to the transplanted tumor cells may not be the reason that the tumor ascites did not form in the mice with tumor cell IUT. Immune tolerance specific for a donor tissue could be used as a foundation for successful IUT, and the process of tolerance induction may lead to reliable and safe methods of prenatal tolerance induction (Ruggeri et al, 2002;Mahieu-Caputo et al, 2004;Chou et al, 2001). The possibility of using IUT to enable xenogeneic organ transplantation is being studied since IUT has been successful in generating chimeras across species barriers (Colas et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Effect of mid‐late mouse fetus' microenvironment on the growth of tumor cells after intrauterine transplantation

Zhou

Fang

et al. 2007

Cell Biology International

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Successful intrauterine transplantation (IUT) of stem cells for treatment of fetal defects in some animal models of human diseases has prompted us to study the mechanisms of transplantation, immunological tolerance and embryonic environment. The objective of this study was to determine whether intrauterine transplantation of tumor cells would affect the survival and growth of the tumor cells themselves as well as fetus development. A total of 2 x 10(6) H(22) cells or S(180) cells were transplanted into the amniotic or abdominal cavity of NIH mice on D9-D12 or D13-D18 of gestation. The adult and newborn NIH mice which were inoculated with the same number of H(22) cells and S(180) cells by intraperitoneal injection were used as positive controls for the cancer bearing control group while undisrupted fetuses of the same gestation were used as negative controls (i.e. for the normal development) group. The development of fetuses transplanted with tumor cells in utero was monitored by several developmental indices, and the tumor growth of them were observed by some distinctive bearing cancer index. The H(22) transplanted group was further assessed for minimal cancer bearing by detection of alpha-fetoprotein (AFP) using radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR). In addition, tumor burden and the development of the F1 generation of the mice by IUT were also investigated. Protein kinase C (PKC) and proliferating cell nuclear antigen (PCNA) of GFP-expressing H(22) cells transplanted in the uterus were analyzed under laser confocal microscopy. There was no significant difference in the developmental indices between the experimental and control groups. HE staining of the major organs, including liver, kidney, and lung, showed that these organs properly developed. No tumor ascites were found in those delivered mice after intrauterine transplantation with H(22) cells and S(180) cells. Furthermore, as minimal bearing cancer index for H(22) cells, AFP expression analyzed by RIA and RT-PCR indicated that no tumor cells were detected in the experimental groups. The F1 progenies developed normally without any signs of tumor development. Fluorescence analysis revealed that expression of PKC and PCNA was markedly reduced in the H(22) cells after injection for 24, 48, and 72 h. Our study showed that the tumor cells did not grow in the mice by intrauterine transplantation, whereas transplantation of the same number of tumor cells resulted in obvious ascites tumor in the adult and newborn mice. Furthermore, the differentiation and proliferation of H(22) cells changed dramatically after injection. Our results suggest that, while the embryonic transplantation of tumor cells does not affect fetal development, the survival and growth of implanted tumor cells may be significantly inhibited in the embryonic microenvironment.

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Section: Discussionmentioning

confidence: 99%

Effect of mid‐late mouse fetus' microenvironment on the growth of tumor cells after intrauterine transplantation

Zhou

Fang

et al. 2007

Cell Biology International

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“…41 Hepatocyte chimerism has also been achieved in non-human primates transplanted with fetal hepatocytes. 42,43 Human mesenchymal stem cells have also been shown to engraft numerous tissues when transplanted in fetal sheep. 44 Mesenchymal stem cells derived from fetal liver have also been transplanted in a case of osteogenesis imperfecta resulting in the detection of 5% donor-derived osteoblasts at 8 months of age (Table 4).…”

Section: Enzyme Storage and Other Diseasesmentioning

confidence: 99%

In utero transplantation: baby steps towards an effective therapy

Muench

2005

Bone Marrow Transplant

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In utero transplantation (IUT) offers the potential to treat a large number of diseases by transplantation of healthy cells into a fetus with a birth defect. Prenatal diagnosis is feasible for many diseases prior to the full development of the fetal immune system offering the opportunity to introduce foreign cells and antigens into the developing fetus. At least 45 cases of IUT have been performed for a variety of diseases. IUT has successfully treated severe combined immunodeficiency and there are indications that it may be effective in treating some nonhematopoietic diseases. However, many diseases remain resistant to fetal therapy owing to the low levels of chimerism that can be achieved. Promising efforts to improve the levels of engraftment are focusing on optimizing the graft and developing donor-specific tolerance in the fetal recipient. Mounting evidence suggests that donor T cells can aid in achieving clinically significant levels of chimerism. The use of fetal donor cells may also offer some benefit. Animal experiments suggest that even low-level chimerism can lead to tolerance, which can be exploited by booster transplants in the neonate. Continued research appears likely to succeed in developing IUT into an effective form of therapy for a variety of diseases.

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“…Furthermore, liver engraftment was observed in some nonhuman primates transplanted with fetal hepatocytes. 155,180,181 For the purpose of producing a specific liver gene product, hepatocytes might not be the only cells that can be transplanted. Takahashi et al 182 used amniotic epithelial cells that were transfected with adenoviral vector and transplanted into fetal rat liver to show that other cell types can be used to deliver gene products to a fetus.…”

Section: In Utero Transplantation Of Nonhematopoietic Cellsmentioning

confidence: 99%