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

SUBMITTER: Chou DB 

PROVIDER: S-EPMC7160021 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature