Abnormal protease-resistant prion protein (PrP-res) is the only Surrogate biochemical marker for prion diseases, and a sensitive technique to detect PrP-res in blood or tissues is urgently needed. Primary cultured bone marrow stromal cells (MSCs) expressed PrP and were capable of supporting stable human prion infection. Using a mouse-adapted BSE strain, we demonstrated that PrP-res can be detected in expanded MSCs. We then analyzed the bone marrow cells collected at autopsy from two individuals with sporadic Creutzfeldt-Jakob disease (CJD), and, in both cases, cultured MSCs were positive for PrP-res. These data would suggest that ex vivo MSC expansion accompanied by PrP-res analysis could be a helpful too] in the definitive diagnosis of prion disease at an earlier stage in the disease process than is currently possible, and with considerably less distress to the patient. (C) 2008 Elsevier Inc. All rights reserved.