Surbek D V, Hohlfeld P, Gratwohl A, Holzgreve W
Universitäts-Frauenklinik Basel.
Z Geburtshilfe Neonatol. 1997 Sep-Oct;201(5):158-70.
In utero transplantation of hematopoietic stem cells is a most promising fetal therapy. The aim is to treat a genetic disease prenatally before the onset of irreversible organ damage. As the fetus is immunoincompetent in the first and early second trimester of pregnancy and thus tolerant to foreign antigen, engraftment of transplanted stem cells is possible without rejection and without the need for immunosuppression. Additionally, there is enough space available in the fetal bone marrow for the homing of transplanted stem cells, and the intrauterine environment is protective for the fetus, thus typical complications of postnatal transplantation like graft rejection could be avoided. Good results of in utero treatment of severe congenital immunodeficiencies have been achieved in different animal models as well as in humans. No success, however, has been reported as yet in genetic diseases without immunodeficiency, mainly because it seems to be difficult to achieve a clinically significant level of chimerism. Ongoing research projects are focussed on the search for alternative stem cell sources like umbilical cord blood or fetal liver, optimizing the in vitro stem cell processing by using special enrichment techniques, adding early growth factors to the transplant or expanding stem cells ex vivo and finding the ideal stem cell dose. In non-immunodeficient recipients the "window of opportunity" seems to be exclusively at the end of the first trimester; thus early administration of the transplant is mandatory. Induction of tolerance against donor cells is possible, though the clinical relevance for postnatal transplantation remains to be proven.
造血干细胞宫内移植是一种极有前景的胎儿治疗方法。其目的是在不可逆的器官损伤发生之前对遗传性疾病进行产前治疗。由于胎儿在妊娠的第一个月和第二个月早期免疫功能不全，因此对异体抗原具有耐受性，移植的干细胞有可能在不发生排斥反应且无需免疫抑制的情况下实现植入。此外，胎儿骨髓中有足够的空间供移植的干细胞归巢，并且子宫内环境对胎儿有保护作用，因此可以避免出生后移植的典型并发症，如移植物排斥反应。在不同的动物模型以及人类中，宫内治疗严重先天性免疫缺陷均取得了良好效果。然而，在非免疫缺陷的遗传性疾病中尚未有成功的报道，主要是因为似乎难以达到临床上显著的嵌合水平。正在进行的研究项目集中在寻找替代干细胞来源，如脐带血或胎儿肝脏；通过使用特殊的富集技术优化体外干细胞处理；在移植中添加早期生长因子或在体外扩增干细胞；以及确定理想的干细胞剂量。在非免疫缺陷受体中，“机会窗口”似乎仅存在于妊娠第一个月末；因此必须尽早进行移植。诱导对供体细胞的耐受性是可能的，不过其对出生后移植的临床相关性仍有待证实。
