![]() On postoperative day #7, CellCept was discontinued and animals were randomly assigned to three groups ( n = 5 per group) to assess three tacrolimus doses: 0.3 mg/kg, 1.5 mg/kg, and 3 mg/kg. On the day of the procedure and daily for 6 days later (seven doses total), 30 mg/kg of mycophenolate mofetil (CellCept Genentech USA Inc., South San Francisco, CA) was administered subcutaneously in conjunction with the tacrolimus. Tacrolimus (FK-506, Prograf ®, Astellas Pharmas US Inc., Northbrook, IL) was administered subcutaneously to all animals at 3 mg/kg starting 2 days prior to surgery and daily until postoperative day #6. Each 1 μL injection was administered over 60 sec, with a 60-sec delay prior to needle withdrawal, at a cell concentration of 30,000 cells/ μL, delivering a total of 180,000 cells per animal. NSCs were administered to 12-week-old mice by three injections into the CC bilaterally at three sites (total six injections), represented by the following atlas coordinates from the bregma (posterior, lateral, ventral): −0.82/(±)0.6/1.9, −1.82/(±)0.6/1.5, −2.3/(±)0.6/1.5 mm, respectively. Research grade human NSCs, NSI-HK532-IGF-I, a modified line we previously characterized, 15 were provided by Neuralstem, Inc. Male Tg-AD B6C3-Tg(APPswe/PSEN1ΔE9)85Dbo/J (APP/PS1) mice were obtained from the Jackson Laboratory (Bar Harbor, ME). 15 Materials and Methods Surgical transplantation of NSCs to the CCĪll procedures were approved by the University of Michigan (U-M) Institutional Animal Care and Use Committee. Here, we assessed optimal immunosuppression and the feasibility of CC targeting with a modified human neural stem cell (NSC) line, which we previously characterized and targeted to the fimbria fornix of AD mice. We therefore hypothesize that the CC is an ideal treatment target for cellular therapies for AD. 9- 11 This, coupled with the fact that stem cells migrate through large white matter tracts, 12- 14 makes the CC a potentially effective target. ![]() CC size changes and atrophy occur in AD patients and correlate with progression of dementia severity. ![]() One of the proposed targets is the corpus callosum (CC), a large white matter tract that includes the neural pathway starting at the nucleus basalis of Meynert, and connects the majority of frontal, parietal, and occipital cortical areas to corresponding regions in the contralateral hemisphere. 1, 7, 8 With the success of hippocampal targeting, interest has grown in identifying other intracranial targets suitable for stem cell transplantation. 1- 6 As such, transplantation of stem cells from various sources into the hippocampus improves cognitive impairment in murine AD models. Cellular therapies represent a potential disease-modifying treatment for Alzheimer's disease (AD), with multifaceted therapeutic benefits including tissue replacement, secretion of neuroprotective trophic factors, and/or modulation of inflammation.
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