Cell-to-cell communication plays an essential role in regulating homeostasis in multicellular organisms. Recent evidence indicates that cells effectively communicate via extracellular vesicles (EVs), which carry bioactive cargo, such as proteins, lipids and RNA, between cells. Advancement in the field produced tremendous information that gives insights into the biological role of EVs in many aspects of physiological and pathophysiological events. Due to their signature content and biocompatibility, EVs represent a potential source of diagnostic tools and therapeutic agents. As well, their use might overcome limitations and risks associated with cell-therapy approaches. Bone is a complex organ consisting of a broad variety of cell types living in harmony within the favorable microenvironment of the bone marrow. The establishment of a proper communication network is key to ensure not only normal bone development but also many other vital physiological processes.
In this thesis, we present a thorough characterization of the biochemical content of EVs secreted by human osteoblasts using omics technologies, such as mass spectrometry and next-generation sequencing. Furthermore, we study the biological significance of regulatory EV cargo in communication with the cells in the surrounding bone microenvironment, in particular with hematopoietic stem and progenitor cells (HSPCs) and bone-metastasizing cancer cells. Ultimately, we investigate the therapeutic potency of osteoblast-EVs in regenerative medicine by evaluating their potential in ex vivo expansion of human umbilical cord blood-derived HSPCs for clinical use.

, , , ,
J.P.T.M. van Leeuwen (Hans) , J.J. Cornelissen (Jan) , J. van de Peppel (Jeroen)
Erasmus University Rotterdam
This work was financially supported by a grant from the Dutch government to the Netherlands Institute for Regenerative Medicine (FES0908), Erasmus MC Stem Cell and Regenerative Medicine Institute and Erasmus University Medical Center. Next-generation RNA sequencing studies were performed in collaboration with the Department of Orthopedic Surgery at Mayo Clinic, Rochester, MN, USA, with the additional financial support provided by the US National Institutes of Health grants (R01-AR049069 and F32-AR066508).
Department of Internal Medicine

Morhayim, J. (2016, September 7). Extracellular Vesicles within the Bone Marrow Niche : A novel way of communication between osteoblasts and hematopoietic progenitor cells. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/93221