A microfluidic bone marrow chip for the safety profiling of biologics in pre-clinical drug development

The overall objective of the study is to evaluate a bone marrow microfluidic system for its ability to predict expected hematopoietic liabilities of immunotherapeutics. The human bone marrow model consists of a zirconium oxide/hyaluronic acid scaffold, primary human stromal cells, and primary human CD34+ hematopoietic stem and progenitor cells. RNA sequencing was used to investigate changes in gene expression signatures of mesenchymal stromal cells when cultured on the ceramic scaffold, when cultured in a hematopoietic culture medium, and when cultured in the microfluidic system. Single donor mesenchymal stromal cells purchased from StemCell Technologies (Cat# 70071) were expanded for two passages in stromal cell culture medium according to the manufacturer's recommendations. The cells were then seeded at 500,000 cells per ceramic scaffold and cultured in 24-well plates for 8 days. The seeded ceramic scaffolds were then either continuously cultured in stromal cell culture medium or switched to hematopoietic cell culture medium after 10 days. Scaffolds cultured in hematopoietic cell culture medium were either continuously cultured under static culture conditions in 24-well plates or placed in the microfluidic system under flow for 24 days.