Characterization of Proteins Released by Osteoblasts That Promote Expansion of Hematopoietic Progenitors

Abstract

Umbilical cord blood (UCB) is a source of hematopoietic stem and progenitor cells (HSPC) used for allogeneic transplantation. Ex vivo expansion of HSPC can improve the slow platelet and neutrophil engraftment associated with UCB transplants. HSPCs reside in niches, some of which are near the endosteal bone surface, where they can associate with immature osteoblasts. Interestingly, osteoblasts can enhance the growth of HSPC in culture and their platelet engraftment activity. Using a proteomics approach, I identified 47 differentially expressed proteins between mesenchymal stem cells and immature osteoblasts. Several of these were previously implicated in HSPC maintenance such as IGF2, IGFBP2, DCN, GAS6 and VCAM1. Moreover, several other proteins belong to the alternative and classical complement pathways. Finally, I discovered that microvesicles found in osteoblast conditioned medium may also modulate the growth of HSPC, at least in ex vivo cultures.