In utero Therapy for the Treatment of Sickle Cell Disease: Taking Advantage of the Fetal Immune System
Open Access
- 22 January 2021
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Sickle Cell Disease (SCD) is an autosomal recessive disorder resulting from a β-globin gene missense mutation and is among the most prevalent severe monogenic disorders worldwide. Haematopoietic stem cell transplantation remains the only curative option for the disease, as most management options focus solely on symptom control. Progress in prenatal diagnosis and fetal therapeutic intervention raises the possibility of in utero treatment. SCD can be diagnosed prenatally in high-risk patients using chorionic villus sampling. Among the possible prenatal treatments, in utero stem cell transplantation (IUSCT) shows the most promise. IUSCT is a non-myeloablative, non-immunosuppressive alternative conferring various unique advantages and may also offer safer postnatal management. Fetal immunologic immaturity could allow engraftment of allogeneic cells before fetal immune system maturation, donor-specific tolerance and lifelong chimerism. In this review, we will discuss SCD, screening and current treatments. We will present the therapeutic rationale for IUSCT, examine the early experimental work and initial human experience, as well as consider primary barriers of clinically implementing IUSCT and the promising approaches to address them.Funding Information
- Academy of Medical Sciences
This publication has 134 references indexed in Scilit:
- Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimatesThe Lancet, 2013
- Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell AnemiaCold Spring Harbor Perspectives in Medicine, 2012
- Glutamine Supplementation in Sick Children: Is It Beneficial?Journal of Nutrition and Metabolism, 2011
- Hematopoietic stem and progenitor cell traffickingTrends in Immunology, 2011
- Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)The Lancet, 2011
- Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in miceJCI Insight, 2011
- Free Heme and the Polymerization of Sickle Cell HemoglobinBiophysical Journal, 2010
- Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in miceJCI Insight, 2009
- Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in UteroScience, 2008
- Redox-dependent impairment of vascular function in sickle cell diseaseFree Radical Biology & Medicine, 2007