Our team has developed a multifaceted approach combining wet and dry lab models to study sepsis mechanisms, which can be used as a clinical tool in the future. Inspired by previous research using organoids as disease models (Khan, et al., 2023) our team has decided to create a human bone marrow organoid to mimic the bone-marrow environment in-vitro to lay the foundation for further immune and sepsis related studies. In conjunction, to further our understanding of the immune system and septic conditions, we built a mechanistic model to simulate and predict hematopoeietc dynamics. Through a series of stepwise, directed-differentiation steps, we will recapitulate bone-marrow conditions in-vitro that display key features of the endosteal and perivascular niche of bone marrow, including myeloid cell lineages affected by sepsis to study the effects of hematopoiesis and immune response in sepsis. The structural and chemical similarity of our organoids to human bone-marrow will allow for further studies of the immune system and septic conditions without harming a living test subject.

To further our understanding of the immune system and septic conditions, we also built an in silico mechanistic model This model allowed us to simplify the complex immune system through differential equations by treating the immune system as a set of nodes that each have a positive or negative “force” on the other nodes. Our model differs from other attempts in literature because it takes into account the number of hematopoietic stem and progenitor cells (HSPCs) along with pro-inflammatory leukocytes and anti-inflammatory leukocytes. Integrating HSPC’s into our model has given us insight into the nature of how the level of stem cells in our immune system can affect the overall immune response.