Jung Yeon Lim1, Sang In Park2, Soon A Park3, Jung Ho Jeon4, Ho Yong Jung2, Jung-Min Yon4, Sin-Soo Jeun3, Hyun Kook Lim5, Sung Won Kim6. 1. Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea. jylim8921@gmail.com. 2. Institute of Catholic Integrative Medicine (ICIM), Incheon St. Mary's Hospital, The Catholic University of Korea, 56 Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea. 3. Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea. 4. Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea. 5. Department of Psychiatry, Yeouido St. Mary's Hospital, The Catholic University of Korea, 63-ro 10, Yeoungdeungpo-gu, Seoul, 07345, Republic of Korea. 6. Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea. kswent@catholic.ac.kr.
Abstract
BACKGROUND: Stem cell transplantation is a fascinating therapeutic approach for the treatment of many neurodegenerative disorders; however, clinical trials using stem cells have not been as effective as expected based on preclinical studies. The aim of this study is to validate the hypothesis that human neural crest-derived nasal turbinate stem cells (hNTSCs) are a clinically promising therapeutic source of adult stem cells for the treatment of Alzheimer's disease (AD). METHODS: hNTSCs were evaluated in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) according to the effect of transplantation on AD pathology, including PET/CT neuroimaging, immune status indicated by microglial numbers and autophagic capacity, neuronal survival, and cognition, in a 5 × FAD transgenic mouse model of AD. RESULTS: We demonstrated that hNTSCs showed a high proliferative capacity and great neurogenic properties in vitro. Compared with hBM-MSC transplantation, hNTSC transplantation markedly reduced Aβ42 levels and plaque formation in the brains of the 5 × FAD transgenic AD mice on neuroimaging, concomitant with increased survival of hippocampal and cortex neurons. Moreover, hNTSCs strongly modulated immune status by reducing the number of microglia and the expression of the inflammatory cytokine IL-6 and upregulating autophagic capacity at 7 weeks after transplantation in AD models. Notably, compared with transplantation of hBM-MSCs, transplantation of hNTSCs significantly enhanced performance on the Morris water maze, with an increased level of TIMP2, which is necessary for spatial memory in young mice and neurons; this difference could be explained by the high engraftment of hNTSCs after transplantation. CONCLUSION: The reliable evidence provided by these findings reveals a promising therapeutic effect of hNTSCs and indicates a step forward the clinical application of hNTSCs in patients with AD.
BACKGROUND: Stem cell transplantation is a fascinating therapeutic approach for the treatment of many neurodegenerative disorders; however, clinical trials using stem cells have not been as effective as expected based on preclinical studies. The aim of this study is to validate the hypothesis that human neural crest-derived nasal turbinate stem cells (hNTSCs) are a clinically promising therapeutic source of adult stem cells for the treatment of Alzheimer's disease (AD). METHODS: hNTSCs were evaluated in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) according to the effect of transplantation on AD pathology, including PET/CT neuroimaging, immune status indicated by microglial numbers and autophagic capacity, neuronal survival, and cognition, in a 5 × FADtransgenicmouse model of AD. RESULTS: We demonstrated that hNTSCs showed a high proliferative capacity and great neurogenic properties in vitro. Compared with hBM-MSC transplantation, hNTSC transplantation markedly reduced Aβ42 levels and plaque formation in the brains of the 5 × FADtransgenicADmice on neuroimaging, concomitant with increased survival of hippocampal and cortex neurons. Moreover, hNTSCs strongly modulated immune status by reducing the number of microglia and the expression of the inflammatory cytokine IL-6 and upregulating autophagic capacity at 7 weeks after transplantation in AD models. Notably, compared with transplantation of hBM-MSCs, transplantation of hNTSCs significantly enhanced performance on the Morris water maze, with an increased level of TIMP2, which is necessary for spatial memory in young mice and neurons; this difference could be explained by the high engraftment of hNTSCs after transplantation. CONCLUSION: The reliable evidence provided by these findings reveals a promising therapeutic effect of hNTSCs and indicates a step forward the clinical application of hNTSCs in patients with AD.
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Authors: Jung Yeon Lim; Jung Eun Lee; Soon A Park; Sang In Park; Jung-Min Yon; Jeong-Ah Park; Sin-Soo Jeun; Seung Joon Kim; Hong Jun Lee; Sung Won Kim; Seung Ho Yang Journal: Cells Date: 2022-03-18 Impact factor: 6.600