Flake A W, Zanjani E D
Children's Institute of Surgical Science, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Ann N Y Acad Sci. 1998 Jun 30;850:300-11. doi: 10.1111/j.1749-6632.1998.tb10487.x.
In utero hematopoietic stem cell transplantation is a promising approach for the treatment of a variety of congenital hematologic diseases. Although the approach has been successful for immunodeficiency syndromes, attempts thus far to treat the hemoglobinopathies have failed. In most of these cases the late gestational age at transplantation, source of donor cells, or procedure-related complications, provide an explanation for failure. Nevertheless the biology of thalassemia, in the context of prenatal transplantation, requires examination. In contrast to postnatal bone marrow transplant regimens, engraftment after in utero transplantation requires donor cells to effectively complete for developing receptive sites in the recipient hematopoietic microenvironment. Effective prenatal treatment of thalassemia will depend on the ability of normal cells to engraft and complete in the thalassemic microenvironment. Clinical observations after bone marrow transplantation of amelioration of anemia in beta-thalassemia by relatively low degrees of mixed chimerism, and the apparent selective advantage observed for donor erythropoiesis, suggest prenatal transplantation could succeed. Prenatal strategies involving multiple transplants, donor-specific tolerance induction, and postnatal same-donor transplants should be considered.
宫内造血干细胞移植是治疗多种先天性血液疾病的一种有前景的方法。尽管该方法已成功用于免疫缺陷综合征的治疗，但迄今为止治疗血红蛋白病的尝试均告失败。在大多数此类病例中，移植时的孕晚期、供体细胞来源或与手术相关的并发症，都为失败提供了解释。然而，在地中海贫血的产前移植背景下，其生物学特性仍需研究。与出生后骨髓移植方案不同，宫内移植后的植入需要供体细胞有效地竞争受体造血微环境中正在发育的接受位点。地中海贫血的有效产前治疗将取决于正常细胞在贫血微环境中植入并完成发育的能力。骨髓移植后相对低程度的混合嵌合体改善β地中海贫血贫血症状的临床观察，以及供体红细胞生成所观察到的明显选择性优势，表明产前移植可能成功。应考虑涉及多次移植、供体特异性耐受诱导和出生后同供体移植的产前策略。
