The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology
Open accessAbstract
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. A vascularized human bone-marrow-on-a-chip improves the maintenance of patient-derived CD34+ cells, and recapitulates clinically relevant aspects of bone marrow injury as well as key haematopoietic defects of patients with a rare genetic disorder.
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Metadata
- Authors
- Chou, D. B., Frismantas, V., Milton, Y., David, R., Pop-Damkov, P., Ferguson, D., MacDonald, A., Vargel Bölükbaşı, Ö., Joyce, C. E., Moreira Teixeira, L. S., Rech, A., Jiang, A., Calamari, E., Jalili-Firoozinezhad, S., Furlong, B. A., O’Sullivan, L. R., Ng, C. F., Choe, Y., Marquez, S., Myers, K. C., Weinberg, O. K., Hasserjian, R. P., Novak, R., Levy, O., Prantil-Baun, R., Novina, C. D., Shimamura, A., Ewart, L., & Ingber, D. E.
- Venue
- Nature Biomedical Engineering
- Published
- 2020-01-27
- Volume
- 4
- Issue
- 4
- Pages
- 394-406
- ISSN
- 2157-846X (ISSN-L)
- OpenAlex
- W3002826985
- Cited by
- 294
- References
- 60
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- green
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- Chou, D. B., Frismantas, V., Milton, Y., David, R., Pop-Damkov, P., Ferguson, D., MacDonald, A., Vargel Bölükbaşı, Ö., Joyce, C. E., Moreira Teixeira, L. S., Rech, A., Jiang, A., Calamari, E., Jalili-Firoozinezhad, S., Furlong, B. A., O’Sullivan, L. R., Ng, C. F., Choe, Y., Marquez, S., . . . Ingber, D. E. (2020). On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nature Biomedical Engineering. https://doi.org/10.1038/s41551-019-0495-z
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
