Hematopoietic stem cells (HSCs) normally reside in the bone marrow niche but can traffic across the bone marrow endothelium into the bloodstream to populate different niches. This process of HSC mobilization from the bone marrow to the blood, is an increasingly favored procedure to obtain HSCs for hematopoietic cell transplantation therapy. Though mobilization is robust in many donors due to years of refined protocols and drug combinations, the process remains difficult or contraindicated among substantial patient subgroups. Using the current standard of care, up to 30% of patients fail to mobilize HSCs and some patients cannot tolerate the current mobilization procedures. Today’s guests will discuss their research using vascular endothelial growth factor, known as VEGF, as an alternative method of mobilization, the mechanisms underlying it, and the implications for improving patient outcomes.

The role of neuronal influences on cancer pathogenesis and progression is increasingly appreciated in the nervous system. Neurons have been shown to enhance the proliferation and migration of gliomas, a glial-derived tumor of the CNS, via diffusible paracrine factors or synaptic inputs onto tumor cells. In glioblastomas, a highly aggressive glioma, mostly glutamatergic inputs have been identified. While the potential for glioblastomas to receive projections from neurons of other neurotransmitter subtypes, such as from cholinergic neurons, has recently been discovered in xenotransplantation models, whether synapses can form between human cholinergic neurons and glioblastoma cells and consequences of these inputs and other non-synaptic mechanisms are still unknown.  

 Human induced pluripotent stem cell-based models have been emerging as a powerful platform for studying human-specific disease mechanisms. Today’s guests developed a co-culture model for the study of neuron-tumor interactions by combining patient derived glioblastoma organoids and hiPSC-derived cholinergic neurons. They will discuss their recent findings and what it means for understanding and potentially treating a tumor for which there is no known cure.