School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, King's College London, United Kingdom.
Immunoregulation Laboratory, School of Immunology, Microbial Sciences, and Faculty of Life Sciences and Medicine, King's College London, United Kingdom.
Stem Cells Dev. 2021 Jan 15;30(2):49-58. doi: 10.1089/scd.2020.0181.
Since its conception, prenatal therapy has been successful in correction of mainly anatomical defects, although the range of application has been limited. Research into minimally invasive fetal surgery techniques and prenatal molecular diagnostics has facilitated the development of in utero stem cell transplantation (IUT)-a method of delivering healthy stem cells to the early gestation fetus with the hope of engraftment, proliferation, and migration to the appropriate hematopoietic compartment. An area of application that shows promise is the treatment of hematopoietic disorders like hemoglobinopathies. The therapeutic rationale of IUT with hematopoietic stem cells (HSCs) is based on the proposed advantages the fetal environment offers based on its unique physiology. These advantages include the immature immune system facilitating the development of donor-specific tolerance, the natural migration of endogenous hematopoietic cells providing space for homing and engraftment of donor cells, and the fetal environment providing HSCs with the same opportunity to survive and proliferate regardless of their origin (donor or host). Maternal immune tolerance to the fetus and placenta also implies that the maternal environment could be accepting of donor cells. In theory, the fetus is a perfect recipient for stem cell transplant. Clinically, however, IUT is yet to see widespread success calling into question these assumptions of fetal physiology. This review aims to discuss and evaluate research surrounding these key assumptions and the clinical success of IUT in the treatment of thalassemia.
自创立以来，产前治疗已成功纠正了主要的解剖缺陷，尽管其应用范围有限。对微创胎儿手术技术和产前分子诊断的研究促进了子宫内干细胞移植（IUT）的发展，这是一种向早期妊娠胎儿输送健康干细胞的方法，希望能植入、增殖并迁移到适当的造血部位。有应用前景的一个领域是治疗血红蛋白病等血液系统疾病。IUT 与造血干细胞（HSCs）的治疗原理基于胎儿环境基于其独特的生理学提供的拟议优势。这些优势包括不成熟的免疫系统有利于发展供者特异性耐受、内源性造血细胞的自然迁移为供体细胞的归巢和植入提供空间，以及胎儿环境为 HSCs 提供了相同的生存和增殖机会，而不受其来源（供者或宿主）的影响。母体对胎儿和胎盘的免疫耐受也意味着母体环境可能接受供体细胞。从理论上讲，胎儿是干细胞移植的完美受体。然而，临床上，IUT 尚未广泛成功，这对胎儿生理学的这些假设提出了质疑。本综述旨在讨论和评估围绕这些关键假设以及 IUT 在治疗地中海贫血症方面的临床成功的研究。
