In utero stem cell transplantation in humans.

Abstract

The prospect of in utero fetal transplantation represents a potential major step forward in the management of patients with congenital hematological, metabolic and immunological disorders. Successful allogeneic in utero transplantations (IUTs) of hematopoietic stem cells HSC) have been reported in several animal models. The first successful transplantation in man was reported by Touraine et al. in 1989 in a case of bare lymphocyte syndrome. Since then more than 35 IUTs have been published or reported at national or international meetings. The transplantations have been reported for a variety of indications, at various gestational ages, and with different sources of the transplant. All cases of IUT performed in fetuses with normal immunological function have failed, and unequivocal engraftment could so far only be demonstrated in fetuses suffering from severe immunodeficiency disorders. Most publications reviewing in utero stem cell transplantation have stated that the fetus is the ideal candidate for therapy due to its immature immune system, which should permit the transplantation of non-human leukocyte antigen (HLA) matched cells and allow the developing fetus to recognize the donor cells as “self” (Flake 1986; Crombleholme et al. 1990, 1991; Flake et al. 1991; Touraine et al. 1991; Zanjani et al. 1991; Zanjani 1992; Westgren and Ringden 1994; Jones et al. 1996; Flake and Zanjani 1997, 1999; Surbek et al. 1999). In addition, there should be abundant and readily available hematopoietic niches from donor cells to engraft secondary to fetal growth. However, when one considers that all attempted allogeneic transplantations in immunocompetent human fetuses have failed, then doubts have to be cast on these theories and the whole concept needs to be reappraised. The purpose of this chapter is to provide a critical review of the clinical progress in this field.