Since stem cell numbers in the graft are important for clinical outcome following transplantation, methods to expand hematopoietic stem cells have been examined extensively. This is particularly relevant in umbilical cord blood (UCB) transplantation, where low numbers of stem cells are directly related to delayed hematopoietic and immune reconstitution.
Improved HSC expansion strategies may significantly impact transplantation outcome, enabling broader applications for UCB transplantation. These strategies are also needed to realize the full therapeutic potential of genome editing technologies to correct hematopoietic stem cells derived from patients with congenital hematologic disorders. Efforts to expand HSCs in cytokine-supported liquid cultures have been largely unsuccessful, and there is now general agreement that efficient expansion requires an appropriate context that is provided by the hematopoietic stem cell niche. A series of research programs will help achieve these important priorities.
|1.1||The assessment of stem cell function is still primarily defined by the cells’ ability to engraft following transplantation. The development of humanized mouse models that predict stem cell function in patients would allow relevant mechanistic studies regarding regulation of stem cell function by the niche.|
|1.2||The process of aging has a negative impact on several HSC functions, including loss of self-renewal potential and homing. A better understanding of the cell-intrinsic as well as environmental mechanisms that underlie aging will aid in the development of novel therapeutic strategies for stem cell transplantation.|
|1.3||Novel expansion procedures rely on the use of cellular support systems (i.e., mesenchymal stem cells) that mimic the niche. Studies must evaluate how niche signals regulate stem cell function to optimize this process for cell expansion.|