Hematopoietic and immune development
Aging is a central and inevitable process. Specifically within our blood cell system, elderly often present with anemia, diminished immune responses and myeloid (rather than lymphoid) blood cell diseases. These suggest altered blood cell formation with age.
Studies in mouse models show that these aging phenotypes, at least in part, can be explained by changes within the most immature blood cell compartments, the hematopoietic stem (HSC) and progenitor cells. One research focus of our group is to expand such studies also to the human system. As such, we have studied aging within the HSC and progenitor cell compartment of aged mice and elderly human and established some conserved age-associated phenotypic, functional and molecular changes, shared among these two species. Currently, we extend these studies to establish some of the mechanisms that drive these processes. Understanding these developmental processes is important to explain, and possibly ameliorate, some of the observed age related diseases.
In addition, knowledge of HSC aging may be of importance on the context of clinical pediatric hematopoietic cell transplantations (HCT). When a pediatric patient receives HSC from an elderly donor, these cells are transplanted across large age-differences and will by far outlive the donor. Does this come at a price? At our clinical Department of Pediatric Oncology/Hematology, haploidentical (haplo-) HCT, where one of the parent acts as donor to his/her child, is routinely used as curative treatment for a number of diseases. These haplo-HCTs serve as a unique and valuable model to study HSC transplantation across large age boundaries. In addition, the fact that parental donors are only 50% HLA-identical impedes on the one hand a risk to develop graft-versus-host disease, but on the other hand it creates an opportunity to induce graft-versus-leukemia actions.
Future work will detail clinical outcome of such pediatric haplo-HCTs. Further, we will use a murine model to study hematological regeneration following haplo-HCT and evaluate how extended graft manipulation impacts graf-versus-leukemia actions. Ultimately, these studies aim to increase HCT efficacy, whilst reducing treatment related complications.