Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases

被引:175
作者
Volkman, Rotem [1 ]
Offen, Daniel [1 ]
机构
[1] Tel Aviv Univ, Tel Aviv, Israel
关键词
Mesenchymal stem cells; Neurodegenerative diseases; Neurotrophic factors; Immunomodulation; Neurogenesis; HUMAN BONE-MARROW; AMYOTROPHIC-LATERAL-SCLEROSIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BLOOD-BRAIN-BARRIER; BETA-AMYLOID CLEARANCE; CENTRAL-NERVOUS-SYSTEM; STROMAL CELLS; MULTIPLE-SCLEROSIS; PARKINSONS-DISEASE; NEUROTROPHIC FACTORS;
D O I
10.1002/stem.2651
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Stem cell-based therapies for neurodegenerative diseases aim at halting clinical deterioration by regeneration and by providing local support for damaged tissue. Mesenchymal stem cells (MSCs) hold great potential for cell therapy as they can be efficiently derived from adult tissue, ex vivo expanded in culture and safely transplanted autologously. MSCs were also shown to be able to differentiate toward neural fates and to secrete a broad range of factors able to promote nervous tissue maintenance and repair. Moreover, upon transplantation, MSCs were shown capable of homing toward lesioned areas, implying their potential use as vehicles for therapeutic agents administration. Indeed, various advantageous effects were reported following human MSCs transplantation into rodent models of neurodegenerative diseases, such as neurotrophic factor-mediated protection, enhanced neurogenesis, modulation of inflammation, and abnormal protein aggregate clearance. Per journal style, most nonstandard abbreviations must be used at least two times in the abstract to be retained; NTF was used once and thus has been deleted. Recent studies have also used ex vivo manipulation for enhanced expression of potentially favorable factors, by so exploiting the homing capacity of MSCs for effective expression at the lesion site. Here, we will summarize current advancements in MSCs-based therapies for neurodegenerative diseases. We will examine the roles of central mechanisms suggested to mediate the beneficial effects of MSCs-based therapy and consider the augmentation of these mechanisms for superior clinical outcomes in rodent models of neurodegeneration as well as in clinical trials.
引用
收藏
页码:1867 / 1880
页数:14
相关论文
共 127 条
[11]   Human mesenchymal stem cells express neural genes, suggesting a neural predisposition [J].
Blondheim, NR ;
Levy, YS ;
Ben-Zur, T ;
Burshtein, A ;
Cherlow, T ;
Kan, I ;
Barzilai, R ;
Bahat-Stromza, M ;
Barhum, Y ;
Bulvik, S ;
Melamed, E ;
Offen, D .
STEM CELLS AND DEVELOPMENT, 2006, 15 (02) :141-164
[12]   Oxidative stress-induced Notch1 signaling promotes cardiogenic gene expression in mesenchymal stem cells [J].
Boopathy, Archana V. ;
Pendergrass, Karl D. ;
Che, Pao Lin ;
Yoon, Young-Sup ;
Davis, Michael E. .
STEM CELL RESEARCH & THERAPY, 2013, 4
[13]   In Vivo Therapeutic Potential of Mesenchymal Stromal Cells Depends on the Source and the Isolation Procedure [J].
Bortolotti, Francesca ;
Ukovich, Laura ;
Razban, Vahid ;
Martinelli, Valentina ;
Ruozi, Giulia ;
Pelos, Barbara ;
Dore, Franca ;
Giacca, Mauro ;
Zacchigna, Serena .
STEM CELL REPORTS, 2015, 4 (03) :332-339
[14]   Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis [J].
Bravo, Beatriz ;
Gallego, Marta I. ;
Flores, Ana I. ;
Bornstein, Rafael ;
Puente-Bedia, Alba ;
Hernandez, Javier ;
de la Torre, Paz ;
Garcia-Zaragoza, Elena ;
Perez-Tavarez, Raquel ;
Grande, Jesus ;
Ballester, Alicia ;
Ballester, Sara .
STEM CELL RESEARCH & THERAPY, 2016, 7
[15]   Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases [J].
Buckner, Jane Hoyt .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (12) :849-859
[16]   Multiple Cell Transplantation Based on an Intraparenchymal Approach for Patients With Chronic Phase Stroke [J].
Chen, Lin ;
Xi, Haitao ;
Huang, Hongyun ;
Zhang, Feng ;
Liu, Yancheng ;
Chen, Di ;
Xiao, Juan .
CELL TRANSPLANTATION, 2013, 22 :S83-S91
[17]   Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1α [J].
Cho, KJ ;
Trzaska, KA ;
Greco, SJ ;
McArdle, J ;
Wang, FS ;
Ye, JH ;
Rameshwar, P .
STEM CELLS, 2005, 23 (03) :383-391
[18]   Adipose-Derived Mesenchymal Stem Cells Reduce Neuronal Death After Transient Global Cerebral lschemia Through Prevention of Blood-Brain Barrier Disruption and Endothelial Damage [J].
Chung, Tae Nyoung ;
Kim, Jin Hee ;
Choi, Bo Young ;
Chung, Sung Phil ;
Kwon, Sung Won ;
Suh, Sang Won .
STEM CELLS TRANSLATIONAL MEDICINE, 2015, 4 (02) :178-185
[19]   Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study [J].
Connick, Peter ;
Kolappan, Madhan ;
Crawley, Charles ;
Webber, Daniel J. ;
Patani, Rickie ;
Michell, Andrew W. ;
Du, Ming-Qing ;
Luan, Shi-Lu ;
Altmann, Daniel R. ;
Thompson, Alan J. ;
Compston, Alastair ;
Scott, Michael A. ;
Miller, David H. ;
Chandran, Siddharthan .
LANCET NEUROLOGY, 2012, 11 (02) :150-156
[20]   Adipose-Derived Mesenchymal Stem Cells Ameliorate Chronic Experimental Autoimmune Encephalomyelitis [J].
Constantin, Gabriela ;
Marconi, Silvia ;
Rossi, Barbara ;
Angiari, Stefano ;
Calderan, Laura ;
Anghileri, Elena ;
Gini, Beatrice ;
Bach, Simone Dorothea ;
Martinello, Marianna ;
Bifari, Francesco ;
Galie, Mirco ;
Turano, Ermanna ;
Budui, Simona ;
Sbarbati, Andrea ;
Krampera, Mauro ;
Bonetti, Bruno .
STEM CELLS, 2009, 27 (10) :2624-2635