In utero stem cell transplantation (IUTx) is a therapeutic option for some lymphohaematopoietic disorders which can be diagnosed early in pregnancy. However, the promise of effective treatment before potentially life-threatening pathology becomes manifested has not been realised in all cases. This has prompted investigators to reassess their understanding of fetal haematopoiesis and of developmental pathways in the fetal immune system, to unravel the problem of failure to engraft after IUTx. The European Network for Fetal Transplantation (ENFET) was established to address these issues and to develop a concerted approach to IUTx. In this way, ENFET aims to study the basic biology of stem cell development and to put the findings into the context of engraftment potential following IUTx. One issue which has gained currency since ENFET was established, is the concept of stem cell ‘plasticity’, which has changed our view of the utility of IUTx so that there is now a real prospect for using this therapy in a larger range of disorders than was initially envisaged. Paradoxically, our current knowledge of stem cell plasticity must also change our views on the utility of IUTx for haematopoietic disorders, since it might offer some insights into the reasons for lack of engraftment observed in some of these conditions. The issue of in utero gene therapy is also being addressed by members of the ENFET consortium. Recent setbacks in postnatal gene therapy trials have put this therapeutic modality under intense scrutiny and there is much work still to be done before such therapy can realistically be offered in utero.

Keywords:
Fetus, Fetal haematopoiesis, In utero transplant, Stem cell
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© 2004 S. Karger AG, Basel
2004
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