In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: Feasibility and short-term follow-up

Andreoletti, Marion; Lepercq, J.; Loux, Nathalie; Beaudoın, Sylvie; Sacquin, P; Borgnon, Joséphine; Nguyen, Tuan Huy; Mahieu, Dominique; Toubas, F; Rico, Virginie Di; Farge, Denis; Franco, Dominique; Briand, Pascale; Hamza, J.; Capron, Frédérique; Bargy, F.; Weber, Anne

doi:10.1002/(sici)1520-6661(199811/12)7:6<296::aid-mfm8>3.0.co;2-w

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Attempts to colonize the fetal liver in order to generate adult animals with chimeric livers have employed mature hepatocytes, oval cells from regenerating livers, or late stage embryonic fetal liver cells transplanted into late stage fetuses [15,29,30]. As these approaches have met with little success, we explored the strategy of injecting midgestation fetal liver cells into midgestation fetuses.…”

Section: Resultsmentioning

confidence: 99%

“…Cellular transplantation into immunocompetent animals still presents the immunological complications associated with organ transplantation. To overcome this problem, it is possible to transplant cells in utero into embryos before the development of immune competence [15]. Cells introduced before immunologic determination of ‘self’ will be incorporated into the developing fetus and should not elicit an immunologic response after the maturation of the immune system.…”

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confidence: 99%

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In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses

Rosen

Cornelissen

Zhong

et al. 2003

Journal of Thrombosis and Haemostasis

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Summary. Factor X (FX)-deficient embryos suffer partial embryonic lethality with approximately 30% of the embryos arresting at midgestation. The remaining animals survive to term but die perinatally mainly from abdominal or intracranial hemorrhage. We have rescued FX-deficient mice by transplanting fetal liver cells from FXþ/þ, Rosa26 fetuses into midgestation embryos derived from FXþ/À heterozygous crosses. FXÀ/À embryos were born at the expected frequency and approximately 50% of the FXÀ/À neonates survived longer than 4 months. FXÀ/À embryos receiving saline injections that survived to term died perinatally similar to untreated FXdeficient mice. The plasma levels of FX in the rescued 16-week-old FXÀ/À mice were approximately 1-6% of wild-type levels. b-Galactosidase-staining cells derived from the donor Rosa26 fetal liver cells were detected in 47% of the livers of adult mice. In addition, donor-derived cells were also recovered in the bone marrow, spleen, lung, and occasionally in the brain and testis. These results suggest that in utero cell transplantation could be an effective therapeutic strategy to treat pathologies resulting from the deficiency of hepatic-expressed factors.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses

Rosen

Cornelissen

Zhong

et al. 2003

Journal of Thrombosis and Haemostasis

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“…As we know, the fetal immune system is not mature, and the mother mice pass the immune function to the fetuses by placental transmission (Andreoletti et al, 1998;Kim et al, 1998) that could not kill the tumor cells, because the pregnant mice on different stages developed obviously cancerous ascites after tumor cells were injected into abdominal cavity with the same number of cancer cells (data not shown). 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.…”

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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“…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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In utero allotransplantation of retrovirally transduced fetal hepatocytes in primates: Feasibility and short-term follow-up

Cited by 8 publications

References 21 publications

In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses

In utero transplantation of wild-type fetal liver cells rescues factor X-deficient mice from fatal neonatal bleeding diatheses

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

In utero transplantation: baby steps towards an effective therapy

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