@article{681,
  keywords = {Biological models, Biomimetics, Drug development, Experimental models of disease, Haematological diseases},
  author = {David B. Chou and Viktoras Frismantas and Yuka Milton and Rhiannon David and Petar Pop-Damkov and Douglas Ferguson and Alexander MacDonald and Özge Vargel Bölükbaşı and Cailin E. Joyce and Liliana S. Moreira Teixeira and Arianna Rech and Amanda Jiang and Elizabeth Calamari and Sasan Jalili-Firoozinezhad and Brooke A. Furlong and Lucy R. O’Sullivan and Carlos F. Ng and Youngjae Choe and Susan Marquez and Kasiani C. Myers and Olga K. Weinberg and Robert P. Hasserjian and Richard Novak and Oren Levy and Rachelle Prantil-Baun and Carl D. Novina and Akiko Shimamura and Lorna Ewart and Donald E. Ingber},
  title = {On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology},
  abstract = {The inaccessibility of living bone marrow (BM) hampers the study of its pathophysiology under myelotoxic stress induced by drugs, radiation or genetic mutations. Here, we show that a vascularized human BM-on-a-chip (BM chip) supports the differentiation and maturation of multiple blood cell lineages over 4 weeks while improving CD34+ cell maintenance, and that it recapitulates aspects of BM injury, including myeloerythroid toxicity after clinically relevant exposures to chemotherapeutic drugs and ionizing radiation, as well as BM recovery after drug-induced myelosuppression. The chip comprises a fluidic channel filled with a fibrin gel in which CD34+ cells and BM-derived stromal cells are co-cultured, a parallel channel lined by human vascular endothelium and perfused with culture medium, and a porous membrane separating the two channels. We also show that BM chips containing cells from patients with the rare genetic disorder Shwachman–Diamond syndrome reproduced key haematopoietic defects and led to the discovery of a neutrophil maturation abnormality. As an in vitro model of haematopoietic dysfunction, the BM chip may serve as a human-specific alternative to animal testing for the study of BM pathophysiology.},
  year = {2020},
  journal = {Nature Biomedical Engineering},
  volume = {4},
  pages = {394-406},
  month = {2020-04},
  issn = {2157-846X},
  url = {https://www.nature.com/articles/s41551-019-0495-z},
  doi = {10.1038/s41551-019-0495-z},
  language = {en},
}