Targeting the Hematopoietic Stem Cell Niche in β-Thalassemia and Sickle Cell Disease

Abstract

In the last decade, research on pathophysiology and therapeutic solutions for β-thalassemia (BThal) and sickle cell disease (SCD) has been mostly focused on the primary erythroid defect, thus neglecting the study of hematopoietic stem cells (HSCs) and bone marrow (BM) microenvironment. The quality and engraftment of HSCs depend on the BM microenvironment, influencing the outcome of HSC transplantation (HSCT) both in allogeneic and in autologous gene therapy settings. In BThal and SCD, the consequences of severe anemia alter erythropoiesis and cause chronic stress in different organs, including the BM. Here, we discuss the recent findings that highlighted multiple alterations of the BM niche in BThal and SCD. We point out the importance of improving our understanding of HSC biology, the status of the BM niche, and their functional crosstalk in these disorders towards the novel concept of combined therapies by not only targeting the genetic defect, but also key players of the HSC–niche interaction in order to improve the clinical outcomes of transplantation.

Drug Design and Development for Rare Hematologic Diseases

“…They focus on the pharmacologic agents for HbF induction that have been developed, starting from a deep understanding of globin regulation. The role of the hematopoietic niche in hemoglobinopathies is further addressed by Aprile et al [8], who discuss the recent findings highlighting multiple alterations of the marrow microenvironment and their functional implications. In particular, they describe the possible role of targeting the bone marrow niche by ameliorating the quality of patient-derived stem cells to improve the effect of gene therapy.…”