Transplantation of Induced Pluripotent Stem Cells Improves Functional Recovery in Huntington's Disease Rat Model

被引：44

作者：

Mu, Shuhua ^{[1
,2
]}

Wang, Jiachuan ^{[2
]}

Zhou, Guangqian ^{[2
]}

Peng, Wenda ^{[1
]}

He, Zhendan ^{[2
]}

Zhao, Zhenfu ^{[2
]}

Mo, CuiPing ^{[2
]}

Qu, Junle ^{[1
]}

Zhang, Jian ^{[1
,2
]}

机构：

[1] Shenzhen Univ, Coll Optoelect Engn, Shenzhen, Peoples R China

[2] Shenzhen Univ, Sch Med, Shenzhen, Peoples R China

来源：

PLOS ONE | 2014年 / 9卷 / 07期

基金：

美国国家科学基金会;

关键词：

SPINAL-CORD-INJURY; INDUCED NEUROPROTECTION; NEURAL TRANSPLANTATION; EXCITOTOXIC LESION; BRAIN; PET; METABOLISM; EXPRESSION; THERAPY; MOTOR;

D O I：

10.1371/journal.pone.0101185

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：

The purpose of this study was to determine the functional recovery of the transplanted induced pluripotent stem cells in a rat model of Huntington's disease with use of F-18-FDG microPET/CT imaging. Methods: In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle ten days after the quinolinic acid injection. The response to the treatment was evaluated by serial F-18-FDG PET/CT scans and Morris water maze test. Histological analyses and Western blotting were performed six weeks after stem cell transplantation. Results: After induced pluripotent stem cells transplantation, higher F-18-FDG accumulation in the injured striatum was observed during the 4 to 6-weeks period compared with the quinolinic acid-injected group, suggesting the metabolic recovery of injured striatum. The induced pluripotent stem cells transplantation improved learning and memory function (and striatal atrophy) of the rat in six week in the comparison with the quinolinic acid-treated controls. In addition, immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated into the lesioned area in striatum, and most of the stem cells expressed protein markers of neurons and glial cells. Conclusion: Our findings show that induced pluripotent stem cells can survive, differentiate to functional neurons and improve partial striatal function and metabolism after implantation in a rat Huntington's disease model.

引用

页数：10

共 45 条

[1] Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain [J].

Acarin, L ;

González, B ;

Castellano, B .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (10) :3505-3520

[2] Striatal glucose metabolism and dopamine D-2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease [J].

Antonini, A ;

Leenders, KL ;

Spiegel, R ;

Meier, D ;

Vontobel, P ;

WeigellWeber, M ;

SanchezPernaute, R ;

deYebenez, JG ;

Boesiger, P ;

Weindl, A ;

Maguire, RP .

BRAIN, 1996, 119 :2085-2095

[3] Deficits in striatal dopamine D2 receptors and energy metabolism detected by in vivo MicroPET imaging in a rat model of Huntington's disease [J].

Araujo, DM ;

Cherry, SR ;

Tatsukawa, KJ ;

Toyokuni, T ;

Kornblum, HI .

EXPERIMENTAL NEUROLOGY, 2000, 166 (02) :287-297

[4] Neuronal replacement from endogenous precursors in the adult brain after stroke [J].

Arvidsson, A ;

Collin, T ;

Kirik, D ;

Kokaia, Z ;

Lindvall, O .

NATURE MEDICINE, 2002, 8 (09) :963-970

[5] Motor and cognitive improvements in patients with Huntington's disease after neural transplantation [J].

Bachoud-Lévi, A ;

Rémy, P ;

Nguyen, JP ;

Brugières, P ;

Lefaucheur, JP ;

Bourdet, C ;

Baudic, S ;

Gaura, V ;

Maison, P ;

Haddad, B ;

Boissé, MF ;

Grandmougin, T ;

Jény, R ;

Bartolomeo, P ;

Dalla Barba, G ;

Degos, JD ;

Lisovoski, F ;

Ergis, AM ;

Pailhous, E ;

Cesaro, P ;

Hantraye, P ;

Peschanski, M .

LANCET, 2000, 356 (9246) :1975-1979

[6] Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4 [J].

Benner, Eric J. ;

Luciano, Dominic ;

Jo, Rebecca ;

Abdi, Khadar ;

Paez-Gonzalez, Patricia ;

Sheng, Huaxin ;

Warner, David S. ;

Liu, Chunlei ;

Eroglu, Cagla ;

Kuo, Chay T. .

NATURE, 2013, 497 (7449) :369-+

[7] NEUROBIOLOGY - BETTER CELLS FOR BRAIN REPAIR [J].

BJORKLUND, A .

NATURE, 1993, 362 (6419) :414-415

[8] Glial cell survival is enhanced during melatonin-induced neuroprotection against cerebral ischemia [J].

Borlongan, CV ;

Yamaoto, M ;

Takei, N ;

Kumazaki, M ;

Ungsuparkorn, C ;

Hida, H ;

Sanberg, PR ;

Nishino, H .

FASEB JOURNAL, 2000, 14 (10) :1307-1317

[9] Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways [J].

Chung, Won-Suk ;

Clarke, Laura E. ;

Wang, Gordon X. ;

Stafford, Benjamin K. ;

Sher, Alexander ;

Chakraborty, Chandrani ;

Joung, Julia ;

Foo, Lynette C. ;

Thompson, Andrew ;

Chen, Chinfei ;

Smith, Stephen J. ;

Barres, Ben A. .

NATURE, 2013, 504 (7480) :394-+

[10] GLIAL CHANGES FOLLOWING AN EXCITOTOXIC LESION IN THE CNS .2. ASTROCYTES [J].

DUSART, I ;

MARTY, S ;

PESCHANSKI, M .

NEUROSCIENCE, 1991, 45 (03) :541-549

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