The Preventive and Therapeutic Effects of Intravenous Human Adipose-Derived Stem Cells in Alzheimer's Disease Mice

被引：108
作者：
Kim, Saeromi [1 ]
Chang, Keun-A [1 ,4 ]
Kim, Jeong A. [1 ]
Park, Hyeong-Geun [2 ]
Ra, Jeong Chan [2 ]
Kim, Hye-Sun [1 ]
Suh, Yoo-Hun [1 ,3 ]
机构：
[1] Seoul Natl Univ, Coll Med, Neurosci Res Inst, MRC,Dept Pharmacol, Seoul, South Korea
[2] RNL Bio Co Ltd, Stem Cell Res Ctr, Seoul, South Korea
[3] Korea Brain Res Inst, Taegu, South Korea
[4] Gachon Univ Med & Sci, Dept Pharmacol, Inchon, South Korea
来源：
PLOS ONE | 2012年 / 7卷 / 09期
基金：
新加坡国家研究基金会;
关键词：
STROMAL CELLS; NEURONAL DIFFERENTIATION; NEUROTROPHIC FACTORS; TRANSGENIC MODEL; AMYLOID-PROTEIN; NERVOUS-SYSTEM; GROWTH-FACTOR; MOUSE MODEL; IN-VITRO; TRANSPLANTATION;
D O I：
10.1371/journal.pone.0045757
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques and neurofibrillary tangles accompanied by cognitive dysfunction. The aim of the present study was to elucidate preventive and therapeutic potential of stem cells for AD. Among stem cells, autologous human adipose-derived stem cells (hASCs) elicit no immune rejection responses, tumorigenesis, or ethical problems. We found that intravenously transplanted hASCs passed through the BBB and migrated into the brain. The learning, memory and pathology in an AD mouse model (Tg2576) mice greatly improved for at least 4 months after intravenous injection of hASC. The number of amyloid plaques and A beta levels decreased significantly in the brains of hASC-injected Tg mice compared to those of Tg-sham mice. Here, we first report that intravenously or intracerebrally transplanted hASCs significantly rescues memory deficit and neuropathology, in the brains of Tg mice by upregulating IL-10 and VEGF and be a possible use for the prevention and treatment of AD.
引用
收藏
页数：17
相关论文
共 41 条
[31]   The therapeutic potential of neural stem cells [J].
Martino, G ;
Pluchino, S .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (05) :395-406
[32]   The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain [J].
Mathieu, Patricia ;
Battista, Daniela ;
Depino, Amaicha ;
Roca, Valeria ;
Graciarena, Mariana ;
Pitossi, Fernando .
JOURNAL OF NEUROCHEMISTRY, 2010, 112 (06) :1368-1385
[33]   ACTIVATION OF MICROGLIAL CELLS BY BETA-AMYLOID PROTEIN AND INTERFERON-GAMMA [J].
MEDA, L ;
CASSATELLA, MA ;
SZENDREI, GI ;
OTVOS, L ;
BARON, P ;
VILLALBA, M ;
FERRARI, D ;
ROSSI, F .
NATURE, 1995, 374 (6523) :647-650
[34]   Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease [J].
Oddo, S ;
Caccamo, A ;
Kitazawa, M ;
Tseng, BP ;
LaFerla, FM .
NEUROBIOLOGY OF AGING, 2003, 24 (08) :1063-1070
[35]   Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury [J].
Park, Kook In ;
Himes, B. Timothy ;
Stieg, Philip E. ;
Tessler, Alan ;
Fischer, Itzhak ;
Snyder, Evan Y. .
EXPERIMENTAL NEUROLOGY, 2006, 199 (01) :179-190
[36]  
Ra JC, 2011, SAFETY INTRAVENOUS I
[37]   Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells [J].
Rehman, J ;
Traktuev, D ;
Li, JL ;
Merfeld-Clauss, S ;
Temm-Grove, CJ ;
Bovenkerk, JE ;
Pell, CL ;
Johnstone, BH ;
Considine, RV ;
March, KL .
CIRCULATION, 2004, 109 (10) :1292-1298
[38]   Alzheimer's disease: Genes, proteins, and therapy [J].
Selkoe, DJ .
PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :741-766
[39]   Neural stem cells improve memory in an inducible mouse model of neuronal loss [J].
Yamasaki, Tritia R. ;
Blurton-Jones, Mathew ;
Morrissette, Debbi A. ;
Kitazawa, Masashi ;
Oddo, Salvatore ;
LaFerla, Frank M. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (44) :11925-11933
[40]   Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10 [J].
Yang, Seung-Ha ;
Park, Min-Jung ;
Yoon, Il-Hee ;
Kim, Su-Young ;
Hong, So-Hee ;
Shin, Jin-Young ;
Nam, Hye-Young ;
Kim, Yong-Hee ;
Kim, Bongi ;
Park, Chung-Gyu .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2009, 41 (05) :315-324
12345