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Statements

Subject Item
n2:RIV%2F67985904%3A_____%2F14%3A00439427%21RIV15-TA0-67985904
rdf:type
n5:Vysledek skos:Concept
dcterms:description
An important component for successful translation of cell replacement-based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large-scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques. The pig model (naive noninjured animals) was recently used successfully to define the safety and optimal dosing of human spinal stem cells after grafting into the central nervous system (CNS) in immunosuppressed animals. The data from these studies were used in the design of a human clinical protocol used in amyotrophic lateral sclerosis (ALS) patients in a Phase I clinical trial. In addition, a highly inbred (complete major histocompatibility complex [MHC] match) strain of miniature pigs is available which permits the design of comparable MHC combinations between the donor cells and the graft recipient as used in human patients. Jointly, these studies show that the pig model can represent an effective large animal model to be used in preclinical cell replacement modeling. This review summarizes the available pig models of neurodegenerative disorders and the use of some of these models in cell replacement studies. The challenges and potential future directions in more effective use of the pig neurodegenerative models are also discussed. An important component for successful translation of cell replacement-based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large-scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques. The pig model (naive noninjured animals) was recently used successfully to define the safety and optimal dosing of human spinal stem cells after grafting into the central nervous system (CNS) in immunosuppressed animals. The data from these studies were used in the design of a human clinical protocol used in amyotrophic lateral sclerosis (ALS) patients in a Phase I clinical trial. In addition, a highly inbred (complete major histocompatibility complex [MHC] match) strain of miniature pigs is available which permits the design of comparable MHC combinations between the donor cells and the graft recipient as used in human patients. Jointly, these studies show that the pig model can represent an effective large animal model to be used in preclinical cell replacement modeling. This review summarizes the available pig models of neurodegenerative disorders and the use of some of these models in cell replacement studies. The challenges and potential future directions in more effective use of the pig neurodegenerative models are also discussed.
dcterms:title
Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies
skos:prefLabel
Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies
skos:notation
RIV/67985904:_____/14:00439427!RIV15-TA0-67985904
n3:aktivita
n17:P n17:I
n3:aktivity
I, P(ED2.1.00/03.0124), P(TA01011466)
n3:cisloPeriodika
12
n3:dodaniDat
n6:2015
n3:domaciTvurceVysledku
n4:4536096 n4:1947788 n4:5434505
n3:druhVysledku
n16:J
n3:duvernostUdaju
n14:S
n3:entitaPredkladatele
n11:predkladatel
n3:idSjednocenehoVysledku
36636
n3:idVysledku
RIV/67985904:_____/14:00439427
n3:jazykVysledku
n18:eng
n3:klicovaSlova
pig; neurodegenerative models; stem cells
n3:klicoveSlovo
n9:stem%20cells n9:neurodegenerative%20models n9:pig
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[187FA0226E89]
n3:nazevZdroje
Journal of Comparative Neurology
n3:obor
n13:FH
n3:pocetDomacichTvurcuVysledku
3
n3:pocetTvurcuVysledku
18
n3:projekt
n8:TA01011466 n8:ED2.1.00%2F03.0124
n3:rokUplatneniVysledku
n6:2014
n3:svazekPeriodika
522
n3:tvurceVysledku
Doležalová, D. Cunningham, M. Bui, J. D. Juhásová, Jana Hazel, T. Muotri, A. Marsala, M. Motlík, Jan Hruška-Plocháň, M. Hefferan, M. P. Sorensen, J. C. H. Juhás, Štefan Ciacci, J. D. Bjarkam, C. R. Johe, K. Strnádel, J. Weingarten, D. Carromeu, C.
n3:wos
000337791000008
s:issn
0021-9967
s:numberOfPages
18
n15:doi
10.1002/cne.23575