In-Utero Transplantation of Stem Cells in Bare Lymphocyte Syndrome

Touraine, Jean‐Louis; Raudrant, D.; Royo, C.; Rebaud, A; Roncarolo, Maria Grazia; Souillet, G; Philippe, N; Touraine, F.; Bétuel, H

doi:10.1016/s0140-6736(89)92819-5

Cited by 129 publications

(56 citation statements)

References 5 publications

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“…[6][7][8] Considerably better results have been obtained in fetuses affected by immunodeficiency syndromes such as SCID or Bare Lymphocyte diseases. 1,9 These findings raised the possibility that fetuses may develop an allogeneic immune reaction responsible for graft failure. Accordingly, fetal liver HSC were capable of engraftment in syngeneic, but not allogeneic recipient mice, 10 and successful allogeneic in utero transplantation of fetal HSC in sheep and monkeys occurred if both the donor and recipient fetuses were in a preimmune state.…”

Section: Discussionmentioning

confidence: 99%

Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation

Mc¹,

Fecarotta²,

Dieli

et al. 2000

Bone Marrow Transplant

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Summary:The use of hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy, although this approach has provided heterogeneous results. In this paper we have undertaken molecular, phenotypic and functional studies aimed at identifying the presence of fully competent T lymphocytes in samples of fetal livers and cord blood. We found mature VDJ TCR ␤ chain transcripts in fetal liver cells taken from 7 to 16 weeks of gestation and a similar pattern was detected in cord blood cells sampled from 13.5 to 20.5 weeks of gestation. A V␤8 gene sequence comparable to that detected in adult PBMC was found in fetal liver samples at 9 or 17 weeks gestation. PreT␣ message was detected in all samples and its expression decreased in fetal blood samples with increasing gestational age while C␣ message appeared at 9.4 weeks and its expression increased during gestational age. T cell clones obtained from fetal liver cells showed a mature TCR ␣␤ + , CD8 + phenotype and displayed strong alloreactivity against allo-MHC class I molecules. The presence of alloreactive T lymphocytes may explain the failure to engraft in fetuses older than 13 to 16 weeks and may provide insights into fetal liver transplantation. Bone Marrow Transplantation of gestation have been transplanted into fetuses at the 13th to 18th week of gestation. 6-8 Considerably better results have been obtained in fetuses affected by immunodeficiency syndromes such as SCID or Bare Lymphocyte diseases. 1,9 These findings raise the possibility that the fetus may develop an allogeneic immune reaction responsible for graft failure. Accordingly, fetal liver HSC were capable of engraftment in syngeneic, but not allogeneic recipient mice, 10 and successful allogeneic in utero transplantation of fetal HSC in sheep and monkeys occurred if both the donor and recipient fetuses were in a preimmune status. 5 Furthermore, we have recently reported 7 that in utero transplantation of an 18 week fetus with fetal HSC resulted in graft failure and after birth the recipient had a very high cytotoxic T cell precursor (CTLp) frequency against donor cells, thus indicating that generation of an alloimmune response rather than tolerance induction was the effect of the procedure.The development of T lymphocytes starts primarily in the embryonic thymus 11-13 after 8 weeks gestation, where they undergo a complex series of differentiation events leading to the expression of the T cell receptor (TCR) complex. 14 Efficient performance of this program appears to be dependent on cellular interactions between developing thymocytes and thymic stromal components. 15 These cells may then colonize the periphery, including the fetal liver itself, as the presence of phenotypically mature T cells has been demonstrated in 11-13 to 22 week old fetal livers. 16 Moreover, recent studies have shown that the liver is also a site for extrathymic T cell development and maturation. 17 Against this background, we have undertaken molecular, phenotypic ...

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Section: Discussionmentioning

confidence: 99%

Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation

Mc¹,

Fecarotta²,

Dieli

et al. 2000

Bone Marrow Transplant

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“…This demonstrates that ontogenic stage-specific progenitor-microenvironment interactions are important for normal hematopoietic development. In the last several years, FL hematopoietic progenitors have been used for in utero or postnatal transplantation (19,38). Failure of FL BFU-E to differentiate in an ABM microenvironment may have important implications for such transplantations and should be kept in mind when FL transplants into adult recipients are contemplated.…”

Section: Discussionmentioning

confidence: 99%

“…For a number of years, transplantation of hematopoietic stem cells from human FL either in utero or postnatally has been considered for clinical purposes (16)(17)(18)(19)(20). However, it is still unclear if hemotopoietic stem cells from FL can establish normal hematopoiesis in adult hematopoietic organs.…”

Section: Introductionmentioning

confidence: 99%

Soluble factor(s) produced by adult bone marrow stroma inhibit in vitro proliferation and differentiation of fetal liver BFU-E by inducing apoptosis.

Roy¹,

Verfaillie²

1997

J. Clin. Invest.

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“…Since Touraine et al published the first instance of intrauterine transplantation in a human fetus affected by bare lymphocyte syndrome (BLS) in 1989, 2 we are aware of 4 X-SCID intrauterine transplantation cases. [3][4][5] All these fetuses survived and were chimeric at birth.…”

mentioning

confidence: 99%

Intrauterine transplantation

Westgren

2009

Blood

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In-Utero Transplantation of Stem Cells in Bare Lymphocyte Syndrome

Cited by 129 publications

References 5 publications

Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation

Evidence of alloreactive T lymphocytes in fetal liver: implications for fetal hematopoietic stem cell transplantation

Soluble factor(s) produced by adult bone marrow stroma inhibit in vitro proliferation and differentiation of fetal liver BFU-E by inducing apoptosis.

Intrauterine transplantation

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