Ashlin Michell
Predoctoral Trainee
Department of Pharmacology & Regenerative Medicine
Advisor: Salman Khetani, PhD Heading link
Title: Engineered fetal liver models for ex vivo hematopoietic stem cell expansion.
Abstract: Hematopoietic stem cells (HSCs) play a critical role in repopulating the blood and have immense therapeutic potential. Over 20,000 Americans require bone marrow transplants yearly, and the major limitation to improving HSC transplants has been the inability to maintain and expand functional HSCs in vitro. Since HSCs initially expand in the fetal liver during development, and since they can migrate to the adult liver and regenerate during injury, we tested the hypothesis that engineered in vitro liver models could expand functional HSCs ex vivo and maintain their multipotency. We found that the human liver microenvironment can expand functional HSCs. We are now developing a fetal liver model in order to study the expansion and maturation of HSCs in the fetal liver and the microenvironmental cues they receive from fetal hepatoblasts. We are comparing 2D and 3D engineered liver platforms for their stability and ability to expand HSCs in serum-free medium, and we have assessed the hepatoblasts’ differentiation over time in these models. Our next steps include incorporation of fetal liver sinusoidal endothelial cells (LSECs) into the fetal liver model to study their effects on HSCs’ migration to and expansion.