Ksenija Bernau1, Christina M Lewis2, Anna M Petelinsek3, Hélène A Benink4, Chad A Zimprich5, M Elizabeth Meyerand6, Masatoshi Suzuki7, Clive N Svendsen8. 1. University of Wisconsin-Madison, 4325a Veterinary Medicine Building, 2015 Linden Dr., Madison, WI 53706, USA. Electronic address: kbernau@medicine.wisc.edu. 2. University of Wisconsin-Madison, 1005 Wisconsin Institute for Medical Research, 1111 Highland Ave., Madison, WI 53705, USA. Electronic address: cmlewis3@wisc.edu. 3. University of Wisconsin-Madison, 4325a Veterinary Medicine Building, 2015 Linden Dr., Madison, WI 53706, USA. Electronic address: petelinsek@wisc.edu. 4. Promega Corporation, 2800 Woods Hollow Rd., Fitchburg, WI 53711, USA. Electronic address: Helene.benink@promega.com. 5. Promega Corporation, 2800 Woods Hollow Rd., Fitchburg, WI 53711, USA. Electronic address: Chad.Zimprich@promega.com. 6. University of Wisconsin-Madison, 1129 Wisconsin Institute for Medical Research, 1111 Highland Ave., Madison, WI 53705, USA. Electronic address: memeyerand@wisc.edu. 7. University of Wisconsin-Madison, 4124 Veterinary Medicine Building, 2015 Linden Dr., Madison, WI 53706, USA. Electronic address: msuzuki@svm.vetmed.wisc.edu. 8. University of Wisconsin-Madison, 5009 Wisconsin Institute for Medical Research, 1111 Highland Ave., Madison, WI 53705, USA. Electronic address: Clive.svendsen@cshs.org.
Abstract
BACKGROUND: Stem cell therapies appear promising for treating certain neurodegenerative disorders and molecular imaging methods that track these cells in vivo could answer some key questions regarding their survival and migration. Bioluminescence imaging (BLI), which relies on luciferase expression in these cells, has been used for this purpose due to its high sensitivity. NEW METHOD: In this study, we employ BLI to track luciferase-expressing human neural progenitor cells (hNPC(Luc2)) in the rat striatum long-term. RESULTS: We show that hNPC(Luc2) are detectable in the rat striatum. Furthermore, we demonstrate that using this tracking method, surviving grafts can be detected in vivo for up to 12 weeks, while those that were rejected do not produce bioluminescence signal. We also demonstrate the ability to discern hNPC(Luc2) contralateral migration. COMPARISON WITH EXISTING METHODS: Some of the advantages of BLI compared to other imaging methods used to track progenitor/stem cells include its sensitivity and specificity, low background signal and ability to distinguish surviving grafts from rejected ones over the long term while the blood-brain barrier remains intact. CONCLUSIONS: These new findings may be useful in future preclinical applications developing cell-based treatments for neurodegenerative disorders.
BACKGROUND: Stem cell therapies appear promising for treating certain neurodegenerative disorders and molecular imaging methods that track these cells in vivo could answer some key questions regarding their survival and migration. Bioluminescence imaging (BLI), which relies on luciferase expression in these cells, has been used for this purpose due to its high sensitivity. NEW METHOD: In this study, we employ BLI to track luciferase-expressing human neural progenitor cells (hNPC(Luc2)) in the rat striatum long-term. RESULTS: We show that hNPC(Luc2) are detectable in the rat striatum. Furthermore, we demonstrate that using this tracking method, surviving grafts can be detected in vivo for up to 12 weeks, while those that were rejected do not produce bioluminescence signal. We also demonstrate the ability to discern hNPC(Luc2) contralateral migration. COMPARISON WITH EXISTING METHODS: Some of the advantages of BLI compared to other imaging methods used to track progenitor/stem cells include its sensitivity and specificity, low background signal and ability to distinguish surviving grafts from rejected ones over the long term while the blood-brain barrier remains intact. CONCLUSIONS: These new findings may be useful in future preclinical applications developing cell-based treatments for neurodegenerative disorders.
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