In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans

Troeger, Carolyn; Surbek, Daniel; Schöberlein, Andreina; Schatt, Stephan; Dudler, Lisbeth; Hahn, Sinuhe; Holzgreve, Wolfgang (2007). In utero haematopoietic stem cell transplantation. Experiences in mice, sheep and humans. Swiss medical weekly, 137(S155), 14S-19S. Muttenz: EMH Schweizerischer Ärzteverlag

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Early prenatal diagnosis and in utero therapy of certain fetal diseases have the potential to reduce fetal morbidity and mortality. The intrauterine transplantation of stem cells provides in some instances a therapeutic option before definitive organ failure occurs. Clinical experiences show that certain diseases, such as immune deficiencies or inborn errors of metabolism, can be successfully treated using stem cells derived from bone marrow. However, a remaining problem is the low level of engraftment that can be achieved. Efforts are made in animal models to optimise the graft and study the recipient's microenvironment to increase long-term engraftment levels. Our experiments in mice show similar early homing of allogeneic and xenogeneic stem cells and reasonable early engraftment of allogeneic murine fetal liver cells (17.1% donor cells in peripheral blood 4 weeks after transplantation), whereas xenogeneic HSC are rapidly diminished due to missing self-renewal and low differentiation capacities in the host's microenvironment. Allogeneic murine fetal liver cells have very good long-term engraftment (49.9% donor cells in peripheral blood 16 weeks after transplantation). Compared to the rodents, the sheep model has the advantage of body size and gestation comparable to the human fetus. Here, ultrasound-guided injection techniques significantly decreased fetal loss rates. In contrast to the murine in utero model, the repopulation capacities of allogeneic ovine fetal liver cells are lower (0.112% donor cells in peripheral blood 3 weeks after transplantation). The effect of MHC on engraftment levels seems to be marginal, since no differences could be observed between autologous and allogeneic transplantation (0.117% donor cells vs 0.112% donor cells in peripheral blood 1 to 2 weeks after transplantation). Further research is needed to study optimal timing and graft composition as well as immunological aspects of in utero transplantation.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
UniBE Contributor:	Surbek, Daniel, Schoeberlein, Andreina
ISSN:	1424-7860
ISBN:	17874495
Publisher:	EMH Schweizerischer Ärzteverlag
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:52
Last Modified:	05 Dec 2022 14:16
PubMed ID:	17874495
Web of Science ID:	000240515800002
URI:	https://boris.unibe.ch/id/eprint/21855 (FactScience: 16290)