Neural transplantation of human neuroteratocarcinoma (hNT) neurons into ischemic rats. A quantitative dose–response analysis of cell survival and behavioral recovery
Section snippets
Experimental procedures
Animals for these studies were 85 male Sprague–Dawley (Zivic–Miller) rats. These animals received unilateral ischemic lesions to the striatum at eight weeks-of-age by subjecting them to unilateral occlusion of the middle cerebral artery for 1 h.5., 8., 21., 28. One month following lesion, the animals were behaviorally tested using a step-down passive avoidance and motor asymmetry test. Those animals that demonstrated behavioral deficits as a result of the ischemic lesion were randomly assigned
Behavioral results
Behavioral data from both the passive avoidance test and EBST demonstrated that learning and memory performance and motor behavior were impaired by the ischemic insult.
Behavioral recovery
Ischemia-induced dysfunction in passive avoidance learning and memory, and in asymmetrical motor behavior, were significantly improved in animals that received 40×103 hNT neurons or more. The behavioral recovery was seen as early as one month post-transplantation, and persisted throughout the entire three-month test period. The results replicated previous observations demonstrating that transplantation of 40×103 hNT neurons into the striatum of ischemically-damaged rats ameliorated behavioral
Conclusions
The readily available hNT neuron shows greater survival than fetal cells and promotes behavioral recovery in rats with ischemic damage. The hNT neuron, therefore, may prove to be an excellent candidate for the treatment of ischemic damage in human patients.
Acknowledgements
The authors would like to thank Stephan Labaste and Stacy Jones Sinibaldi for their expert technical assistance. This study was supported, in part, by Layton BioScience.
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2016, Stem Cell ResearchCitation Excerpt :In this sense, NT2N neurons maintain their neuronal phenotype after transplantation into the rodent brain (Trojanowski et al., 1993; Kleppner et al., 1995; Baker and Mendez, 2005) and spinal cord (Hartley et al., 1999b; Lee et al., 2000). Furthermore, NT2N grafts have been shown to improve motor deficits in animal models of stroke (Borlongan et al., 1998a,b; Saporta et al., 1999) and Huntington's disease (Hurlbert et al., 1999), making NT2N neurons excellent candidates for cell replacement therapy in neurological disorders (Trojanowski et al., 1997; Lee et al., 2000; Nelson et al., 2002; Borlongan et al., 2006; Hara et al., 2008). Indeed, in a phase I clinical trial on 12 patients with basal ganglia stroke and stable motor deficits, NT2N cells were seen to integrate with the host brain tissue for long periods and with no detectable tumor formation (Kondziolka et al., 2000; Meltzer et al., 2001; Nelson et al., 2002), leading to a Phase II study in 18 patients with basal ganglia infarct (Kondziolka et al., 2005).
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