Proof of Concept Studies Exploring the Safety and Functional Activity of Human Parthenogenetic-Derived Neural Stem Cells for the Treatment of Parkinson's Disease

被引:41
作者
Gonzalez, Rodolfo [1 ]
Garitaonandia, Ibon [1 ]
Crain, Andrew [2 ]
Poustovoitov, Maxim [1 ]
Abramihina, Tatiana [1 ]
Noskov, Alexander [1 ]
Jiang, Chuan [3 ]
Morey, Robert [3 ]
Laurent, Louise C. [3 ]
Elsworth, John D. [4 ,5 ,6 ]
Snyder, Evan Y. [2 ]
Redmond, D. Eugene, Jr. [4 ,5 ,6 ]
Semechkin, Ruslan [1 ]
机构
[1] Int Stem Cell Corp, Carlsbad, CA 92008 USA
[2] Sanford Burnham Med Res Inst, La Jolla, CA USA
[3] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA USA
[4] Axion Res Fdn, Hamden, CT USA
[5] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA
[6] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA
关键词
Parthenogenetic stem cells; Neural stem cells (NSCs); Parkinson's disease (PD); DOPAMINERGIC-NEURONS; PRIMATE MODEL; PCR METHOD; TRANSPLANTATION; RECOVERY; PATIENT; GRAFTS;
D O I
10.3727/096368915X687769
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Recent studies indicate that human pluripotent stem cell (PSC)-based therapies hold great promise in Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying viable human embryos and can be used to generate an unlimited supply of neural stem cells for transplantation. Here we evaluate for the first time the safety and engraftment of human parthenogenetic stem cell-derived neural stem cells (hpNSCs) in two animal models: 6-hydroxydopamine (6-OHDA)-lesioned rodents and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated nonhuman primates (NHPs). In both rodents and nonhuman primates, we observed successful engraftment and higher dopamine levels in hpNSC-transplanted animals compared to vehicle control animals, without any adverse events. These results indicate that hpNSCs are safe, well tolerated, and could potentially be a source for cell-based therapies in PD.
引用
收藏
页码:681 / 690
页数:10
相关论文
共 36 条
[1]   Differential expression analysis for sequence count data [J].
Anders, Simon ;
Huber, Wolfgang .
GENOME BIOLOGY, 2010, 11 (10)
[2]   Sensitive PCR method for the detection and real-time quantification of human cells in xenotransplantation systems [J].
Becker, M ;
Nitsche, A ;
Neumann, C ;
Aumann, J ;
Junghahn, I ;
Fichtner, I .
BRITISH JOURNAL OF CANCER, 2002, 87 (11) :1328-1335
[3]   Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson's disease [J].
Bjugstad, Kimberly B. ;
Teng, Yang D. ;
Redmond, D. Eugene, Jr. ;
Elsworth, John D. ;
Roth, Robert H. ;
Cornelius, Shannon K. ;
Snyder, Evan Y. ;
Sladek, John R., Jr. .
EXPERIMENTAL NEUROLOGY, 2008, 211 (02) :362-369
[4]   Gene therapy, cell transplantation and stroke [J].
Borlongan, CV ;
Fournier, C ;
Stahl, CE ;
Yu, GL ;
Xu, L ;
Matsukawa, N ;
Newman, M ;
Yasuhara, T ;
Hara, K ;
Hess, DC ;
Sanberg, PR .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2006, 11 :1090-U46
[5]   INTRACEREBRAL TRANSPLANTATION OF DOPAMINE NEURONS - UNDERSTANDING THE FUNCTIONAL-ROLE OF THE MESOLIMBOCORTICAL DOPAMINE SYSTEM AND DEVELOPING A THERAPY FOR PARKINSONS-DISEASE [J].
BRUNDIN, P ;
STRECKER, RE ;
GAGE, FH ;
LINDVALL, O ;
BJORKLUND, A .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1988, 537 :148-160
[6]   Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice [J].
Cummings, BJ ;
Uchida, N ;
Tamaki, SJ ;
Salazar, DL ;
Hooshmand, M ;
Summers, R ;
Gage, FH ;
Anderson, AJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :14069-14074
[7]   Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys [J].
Elsworth, JD ;
Sladek, JR ;
Taylor, JR ;
Collier, TJ ;
Redmond, DE ;
Roth, RH .
NEUROSCIENCE, 1996, 72 (02) :477-484
[8]   SYMPTOMATIC AND ASYMPTOMATIC 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-TREATED PRIMATES - BIOCHEMICAL-CHANGES IN STRIATAL REGIONS [J].
ELSWORTH, JD ;
DEUTCH, AY ;
REDMOND, DE ;
TAYLOR, JR ;
SLADEK, JR ;
ROTH, RH .
NEUROSCIENCE, 1989, 33 (02) :323-331
[9]  
Elsworth JD, 2000, NEUROSCIENCE, V95, P399
[10]   Intracerebral Transplantation of Differentiated Human Embryonic Stem Cells to Hemiparkinsonian Monkeys [J].
Emborg, Marina E. ;
Zhang, Zhijian ;
Joers, Valerie ;
Brunner, Kevin ;
Bondarenko, Viktorya ;
Ohshima, Sachiko ;
Zhang, Su-Chun .
CELL TRANSPLANTATION, 2013, 22 (05) :831-838