title: Compact MRI for the detection of teratoma development following intrathecal human embryonic stem cell injection in NOD-SCID mice.
abstract: 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.
authors.affiliation: Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.affiliation: Aspect Imaging, Shoham, Israel.
authors.forename: Yael S
authors.initials: YS
authors.lastname: Schiffenbauer
authors.affiliation: Envigo CRS (Israel), Ness Ziona, Israel.
authors.forename: Netanel
authors.initials: N
authors.lastname: Amouyal
authors.affiliation: Envigo CRS (Israel), Ness Ziona, Israel.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ezov
authors.affiliation: Envigo CRS (Israel), Ness Ziona, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Steiner
authors.affiliation: KadimaStem, Ness Ziona, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Izrael
authors.affiliation: KadimaStem, Ness Ziona, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Lavon
authors.affiliation: KadimaStem, Ness Ziona, Israel.
authors.forename: Arik
authors.initials: A
authors.lastname: Hasson
authors.affiliation: KadimaStem, Ness Ziona, Israel.
authors.forename: Michel
authors.initials: M
authors.lastname: Revel
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, and Consultant in Toxicologic Pathology, Timrat, Israel. Electronic address: anyska@bezeqint.net.
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
mesh_terms: D000818:Animals; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging* / Q000209:etiology*; D053595:Embryonic Stem Cells / Q000473:pathology / Q000637:transplantation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009336:Necrosis / Q000473:pathology; D019736:Prostheses and Implants / Q000009:adverse effects; D013724:Teratoma / Q000000981:diagnostic imaging* / Q000209:etiology*; D013997:Time Factors
keywords: MRI; Preclinical safety; Stem cells; Teratoma