@article{bibcite_8866,
  keywords = {Biologics, drug safety, Haematopoiesis, Lab-on-a-chip},
  author = {Leopold Koenig and Laurent Juglair and Thi Phuong Tao and Susanne Fischer and Inga Clausen and Sabine Imhof-Jung and Niels Janssen and Robert Mader and Daniel Marbach and Jens Niewoehner and Annika Winter and Desir{\'e}e Schubert},
  title = {A microfluidic bone marrow chip for the safety profiling of biologics in pre-clinical drug development},
  abstract = {Hematologic adverse events are common dose-limiting toxicities in drug development. Classical animal models for preclinical safety assessment of immunotherapies are often limited due to insufficient cross-reactivity with non-human homologous proteins, immune system differences, and ethical considerations. Therefore, we evaluate a human bone marrow (BM) microphysiological system (MPS) for its ability to predict expected hematopoietic liabilities of immunotherapeutics. The BM-MPS consists of a closed microfluidic circuit containing a ceramic scaffold covered with human mesenchymal stromal cells and populated with human BM-derived CD34+ cells in chemically defined growth factor-enriched media. The model supports on-chip differentiation of erythroid, myeloid and NK cells from CD34+ cells over 31 days. The hematopoietic lineage balance and output is responsive to pro-inflammatory factors and cytokines. Treatment with a transferrin receptor-targeting IgG1 antibody results in inhibition of on-chip erythropoiesis. The immunocompetence of the chip is established by the addition of peripheral blood T cells in a fully autologous setup. Treatment with T cell bispecific antibodies induces T cell activation and target cell killing consistent with expected on-target off-tumor toxicities. In conclusion, this study provides a proof-of-concept that this BM-MPS is applicable for in vitro hematopoietic safety profiling of immunotherapeutics.},
  year = {2025},
  journal = {Communications Biology},
  volume = {8},
  pages = {754},
  month = {2025-05-15},
  issn = {2399-3642},
  url = {https://www.nature.com/articles/s42003-025-08137-1},
  doi = {10.1038/s42003-025-08137-1},
  language = {en},
}