Hematopoietic growth factors including keratinocyte growth factor in allogeneic and autologous stem cell...

The aim of hematopoietic stem cell transplantation (HSCT) is to cure patients of malignancies, autoimmune diseases, and immunodeficiency disorders by redirecting the immune system: the often described graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Unfortunately, fulfillment of this goal is often hampered by relapse of the underlying disease, graft-versus-host disease (GVHD), or severe opportunistic infections, which account for the majority of post-transplantation deaths. Moreover, studies of long-term survivors of transplantation indicate an accelerated immune aging due to the transplantation procedure itself, preceding chemo- or radiotherapy, and acute and chronic GVHD. Significant advances have been made towards overcoming these obstacles by enhancing immune reconstitution with hematopoietic growth factors (HGFs) such as granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) or through the application of cytokines. In addition, there are approaches to promote the thymic-dependent development of naive T cells, which are prepared for the interaction with a multitude of pathogens. Examples are the application of keratinocyte growth factor (KGF), neuroendocrine hormones such as growth hormone or prolactin, sex hormone ablation, or the invention of a three-dimensional artificial thymus based on a cytomatrix. Might these measures result in a higher rate of healthy and fully recovered patients? Here we review progress in each of these areas.