Methods to direct and enrich hematopoietic stem cell engraftment post-transplantation

Abstract

Hematopoietic stem cell transplantation (HSCT) was originally developed as a consequence of undesired toxicity against healthy hematopoietic stem cells (HSCs) while treating malignancies. However, since its inception 70 years ago, HSCT has become a well utilized and diverse tool for the treatment of not just malignant disorders, but monogenic diseases such as hemoglobinopathies and lysosomal storage diseases. The work presented herein aims to explore the engraftment and modification of HSCs through diverse compartments, from the hematopoietic system to the central nervous system. These studies include the modification of the CD33 and CD90 proteins on HSCs paired with their targeting by chimeric antigen receptor (CAR) T-cells in nonhuman primate (NHP) and murine models, as well as more focused studied investigating the engraftment and characterization of microglia-like cells (MLCs) in the NHP brain after HSCT. Finally, I present a snapshot of future directions for works investigating methods to enrich and functionalize MLC engraftment for future therapeutic development.