HUCBC modulation of Alzheimer-like pathology and behavioral changes

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DESCRIPTION (provided by applicant): Modulation of the inflammatory cascade by several diverse strategies including A immunization, non-steroidal anti-inflammatory drug (NSAID) administration, and manipulation of microglial activation states have all been shown to reduce Alzheimer disease (AD)-like pathology, and cognitive deficits in AD transgenic mouse models. Our recent study demonstrated amelioration of AD-like pathology in PSAPP (APPswe, PSEN1dE9) mice when multiply injected with low dose of Saneron's human umbilical cord blood cells mononuclear fraction (HUCBC, trademark name "U-CORD-CELLTM"), a well known immunomodulator. This was observed through marked reduction of A?/?-amyloid plaques and associated astrocytosis. In concert with this down-regulation of pro-inflammatory signaling, cultured microglia isolated from HUCBC-infused PSAPP mice demonstrated increased A? phagocytic activity, thus clearly demonstrating HUCBC's potential immunomodulatory property. Although a typical reduction in cerebral A? plaque burden has been associated with an improvement in cognition, regarded as the true sign of improvement in AD, our study did not address either the behavioral or the cognitive changes associated with HUCBC injections. Thus, in this proposal we would like to test if HUCBC infusion can promote a rescue of behavioral and cognitive deficits and correlate these changes with their pathological improvements in PSAPP mice. Furthermore, we also plan to infuse these mice with human adult mononuclear fractions to demonstrate specific need for HUCBC rather than the adult mononuclear cells in order to observe these immunomodulatory and therapeutic effects. Based on these combined lines of evidence and our recent study, we hypothesize that multiple low dose injections of U-CORD-CELL" into transgenic PSAPP mice will provide a rescue of behavioral deficits, which will be correlated with improvements in AD-like pathology. The goal of this proposal is to establish a strong, well-integrated research program based on recently established roles of Th1/Th2 immunity, HUCBC transplantation, and AD pathogenesis. This knowledge is used to rationalize U-CORD-CELL" as a potentially safe and effective immunomodulatory therapy for AD.Project Narrative - Relevance to public health. In summary, we hypothesize that multiple low dose injections of Saneron's human umbilical cord blood cells mononuclear fraction (HUCBC, trademark name U-CORD-CELL") into transgenic PSAPP mice will provide a rescue of behavioral deficits, which will be correlated with improvements in AD-like pathology. The goal of this proposal is to establish a strong, well-integrated research program based on recently established roles of Th1/Th2 immunity, HUCBC transplantation, and AD pathogenesis. This knowledge is used to rationalize U-CORD-CELL" as a potentially safe and effective immunomodulatory therapy for AD.