Article ID Journal Published Year Pages File Type
5560937 NeuroToxicology 2017 6 Pages PDF
Abstract

•The use of stem cells for CNS disorders is expanding, but there is a risk for teratoma formation.•It is necessary to develop methods for quick detection of teratomas in preclinical safety studies.•MRI allows quick detection of teratomas and provide accurate localization of the tumors.•Compact MRI systems can be used in ordinary labs without the complexity of conventional MRI systems.

Stem cells are emerging as a promising new treatment modality for a variety of central nervous system disorders. However, their use is hampered by the potential for the development of teratomas and other tumors. Therefore, there is a crucial need for the development of methods for detecting teratomas in preclinical safety studies. The aim of the current study is to assess the ability of a compact Magnetic Resonance Imaging (MRI) system to detect teratoma formation in mice. Five NOD-SCID mice were injected intrathecally with human embryonic stem cells (hESCs), with two mice serving as controls. In vivo MRI was performed on days 25 and 48, and ex vivo MRI was performed after scheduled euthanization (day 55). MRI results were compared to histopathology findings. Two animals injected with hESCs developed hind-limb paresis and paralysis, necessitating premature euthanization. MRI examination revealed abnormal pale areas in the spinal cord and brain, which correlated histopathologically with teratomas. This preliminary study shows the efficacy of compact MRI systems in the detection of small teratomas following intrathecal injection of hESCs in a highly sensitive manner. Although these results should be validated in larger studies, they provide further evidence that the use of MRI in longitudinal studies offers a new monitoring strategy for preclinical testing of stem cell applications.

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Life Sciences Environmental Science Health, Toxicology and Mutagenesis
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