Bone marrow stroma cells are susceptible to prion infection

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Abstract

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 tool 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.

Section snippets

Materials and methods

Isolation and culture of MSCs. Adult male Wistar rats, 8 weeks old, were killed and the femurs and tibias were dissected out. Isolation of the bone marrow was performed according to the method described by Azizi et al. [7]. The ends of the bones were cut and the marrow was extruded with 5 ml of alpha-MEM (Sigma, St. Louis, MO) supplemented with 10% fetal bovine serum (FBS), 100 μg/ml kanamycin, or 100 U/ml penicillin and 100 μg/ml streptomycin. The bone marrow cells were incubated at 37 °C with 95%

Results and discussion

MSCs have unique characteristics. They grow well ex vivo without transformation and are multipotential progenitor cells which can be used for auto-cell transplant therapy8. We isolated and subcultured bone marrow cells, and were able to obtain relatively uniform cell types from human, rat and bovine samples, but not from those of mouse and hamster. (Fig. 1A). The rat bone marrow cells grew for more than 2 years (100 passages), but the human cells stopped dividing at about 15 passages, and the

Acknowledgments

We thank Dr. Yasushi Miyazaki, Dr. Hisako Furukawa, and Dr. Susumu Shirabe for support during the CJD patients’ bone marrow biopsies. We thank Dr. T. Yokoyama for providing mouse-BSE agent. We also thank Dr. Norbert Zilka and Dr. Kazuto Shigematsu for helping the experiments. This study was partially supported by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (06-4) and a Grant from the Ministry of Health, Labor and

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