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In utero haematopoietic stem cell transplantation – experimental progress towards clinical application

Alan W Flake
Published in : HAMDAN MEDICAL JOURNAL ; Vol 5, No 3 (2012)
DOI : 10.7707/hmj.v5i3.189


In utero haematopoietic stem cell transplantation (IUHCT) is a potential therapeutic alternative to postnatal allogeneic bone marrow transplantation (BMT) for congenital haematologic disorders that can be diagnosed early in gestation and can be cured by BMT. The rationale is to take advantage of normal events during haematopoietic and immunologic ontogeny to facilitate allogeneic haematopoietic engraftment. The most important of these is the normal process of thymic processing of self-antigen to create a state of self-tolerance. Introduction of allogeneic antigen in the form of haematopoietic stem cells results in a state of permanent donor specific tolerance, eliminating the need for immunosuppression. Although the rationale remains compelling, IUHCT has only been clinically successful in X-linked severe combined immunodeficiency syndrome, a disease in which a competitive advantage exists for donor lymphoid cells. In other disorders, such as the haemoglobinopathies, where host-cell competition is a major barrier, IUHCT has not yet succeeded. However, great experimental progress has recently been made in pre-clinical animal models. Strategies based on prenatal tolerance induction to facilitate post-natal non-toxic cellular transplantation appear promising and clinical application is likely imminent. Because donor specific tolerance induction requires relatively minimal engraftment, this strategy may hold the key to broad clinical application of IUHCT in the near future.

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