Flake A W, Zanjani E D
Department of Surgery, Children's Hospital of Philadelphia, PA 19104, USA.
JAMA. 1997 Sep 17;278(11):932-7.
In utero hematopoietic stem cell transplantation is currently in its early stage of development, but it holds considerable promise as a therapeutic approach for the treatment of a large number of congenital hematologic diseases. Experimental evidence supports the concept of the early gestational fetus as a favorable recipient for cellular therapy. Unique aspects of normal hematologic and immunologic ontogeny allow engraftment and long-term persistence of transplanted hematopoietic stem cells without the requirement for myeloablation or immunosuppression. To date, 21 in utero transplants have been reported. Success has been limited to 4 fetuses, all with immunodeficiency disorders. Despite this limited evidence of clinical efficacy, interest in stem cell transplantation has been gaining momentum, and clinical application is likely to increase. Parallel advances in prenatal diagnosis, fetal intervention, and hematopoietic stem cell technology have removed many of the practical, technical, and ethical obstacles to clinical application. This progress has been accompanied by an increase in the number of centers with both the stated interest and perceived expertise to develop clinical programs. However, there is currently limited consensus among investigators on many important issues, such as the mode or timing of in utero transplantation, the ideal source or dose of donor cells, estimation of maternal and fetal risks, appropriate candidate diseases for treatment, and important ethical considerations in counseling and therapy.
宫内造血干细胞移植目前尚处于发展初期，但作为治疗多种先天性血液疾病的一种治疗方法，它具有相当大的前景。实验证据支持将妊娠早期胎儿作为细胞治疗的理想受体这一概念。正常血液学和免疫学个体发生的独特方面使得移植的造血干细胞能够植入并长期存活，而无需进行骨髓消融或免疫抑制。迄今为止，已报道了21例宫内移植。成功案例仅限于4例胎儿，均患有免疫缺陷疾病。尽管临床疗效的证据有限，但对干细胞移植的兴趣一直在增加，临床应用可能会增多。产前诊断、胎儿干预和造血干细胞技术的同步进展消除了临床应用中的许多实际、技术和伦理障碍。这一进展伴随着既有开展临床项目的兴趣又具备公认专业知识的中心数量的增加。然而，目前研究人员在许多重要问题上的共识有限，如宫内移植的方式或时机、供体细胞的理想来源或剂量、母婴风险评估、适合治疗的候选疾病以及咨询和治疗中的重要伦理考量。
