Combination Strategies for Stem Cell Mobilization Targeting CXCR4 and S1P Receptors

Abstract

Hematopoietic stem cell (HSC) transplantation (HSCT) is now increasingly used to treat a wide range of hematological malignancies as well as certain nonmalignant diseases such as bone marrow failure and immunodeficiency syndromes, metabolic disorders, and autoimmune diseases [1]. In addition, HSC have been investigated for the treatment of ischemic heart disease and stroke, with some encouraging results [2, 3]. The use of mobilized peripheral blood HSC has now largely overtaken that of HSC collected from pelvic bone marrow due to two significant advantages of the former over the latter. Firstly, the collection of mobilized HSC is less invasive, requiring only venous access and leukapheresis, as opposed to the need for general anesthesia and a surgical procedure with a bone marrow harvest. Secondly, there is a higher yield of hematopoietic stem and progenitor cells (as measured by CD34+ cell counts) with mobilized peripheral blood collections than with bone marrow harvests. As a consequence, there is a significant reduction in the duration of both severe neutropenia as well as thrombocytopenia after peripheral blood stem cell transplantation (PBSCT) compared to bone marrow transplantation, with corresponding reductions in toxicity and incidence of serious complications [4]. Peripheral blood stem cells (PBSC) are now used almost exclusively in autologous HSCT, and also in the majority of collections from normal donors for allogeneic HSCT.