(T1040) SSEA3 AND CD105 POSITIVITY ARE ASSOCIATED WITH THE TREATMENT POTENCY OF HUMAN NEURAL CREST-DERIVED NASAL TURBINATE STEM CELLS FOR ALZHEIMER'S DISEASE
postdoctoral fellow Catholic University of Korea, Republic of Korea
Abstract: Stem cells have the potential to treat Alzheimer’s disease (AD), but clinical outcomes are unpredictable due to inter-donor differences in stem cell properties. This study aimed to determine whether the pluripotency marker SSEA3 and the mesenchymal marker CD105 positivity are associated with therapeutic efficacy of human neural crest-derived nasal turbinate stem cells (NTSCs) for AD. The therapeutic effects of NTSCs obtained from different donors, each with varying percentages of SSEA3+/CD105+ cells, were assessed by examining multiple neuropathological changes associated with AD, including the expression of beta-amyloid, inflammation, and neuronal survival. These assessments were conducted in 5×FAD transgenic AD model mice and cerebral organoids derived from induced pluripotent stem cells (iPSC) of three AD patients. Their effects on cognitive functions were measured by performance in the Morris water maze (MWM) test. NTSCs from different donors improved cognitive function and AD-related neuropathology to varying degrees, depending on the percentage of SSEA3+/CD105+ cells. Compared with NTSCs with a lower percentage of SSEA3+/CD105+ cells (NTSCs-L), NTSCs with a higher percentage of SSEA3+/CD105+ cells (NTSCs-H) showed a greater in vitro property, including proliferative capacity, multiple differentiation potency, and secretion of neuroprotective cytokines, which were comparable to pure SSEA3+/CD105+ cells isolated from NTSCs (NTSCs-SC). Both NTSCs-H and NTSCs-SC improved cognitive deficits and reduced cerebral Aβ deposition, inflammation, and neuronal death in AD model mice. Furthermore, NTSCs-H and NTSCs-SC mitigated AD-related pathological features in AD cerebral organoids by decreasing Aβ aggregates, Tau hyperphosphorylation, neuronal death, microglial numbers, and inflammatory cytokine levels. However, there was no significant differences in AD-related pathological changes between NTSCs-H and NTSCs-SC treatment groups. Our findings indicate NTSCs with a high percentage of SSEA3+/CD105+ cells rapidly improve cognitive function and greatly mitigate pathological changes associated with AD, further suggesting that SSEA3/CD105 positivity is a potential marker of NTSCs therapeutic efficacy for the treatment of AD.
Funding Source: This research was supported by the Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI) funded by a grant (RS-2024-00397128) from Ministry of Food and Drug Safety in 2024.
