Document Detail


Induction of pluripotent stem cells from a cynomolgus monkey using a polycistronic simian immunodeficiency virus-based vector, differentiation toward functional cardiomyocytes, and generation of stably expressing reporter lines.
MedLine Citation:
PMID:  23194451     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Abstract Induced pluripotent stem cells (iPSCs) represent a novel cell source for regenerative therapies. Many emerging iPSC-based therapeutic concepts will require preclinical evaluation in suitable large animal models. Among the large animal species frequently used in preclinical efficacy and safety studies, macaques show the highest similarities to humans at physiological, cellular, and molecular levels. We have generated iPSCs from cynomolgus monkeys (Macaca fascicularis) as a segue to regenerative therapy model development in this species. Because typical human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors show poor transduction of simian cells, a simian immunodeficiency virus (SIV)-based vector was chosen for efficient transduction of cynomolgus skin fibroblasts. A corresponding polycistronic vector with codon-optimized reprogramming factors was constructed for reprogramming. Growth characteristics as well as cell and colony morphology of the resulting cynomolgus iPSCs (cyiPSCs) were demonstrated to be almost identical to cynomolgus embryonic stem cells (cyESCs), and cyiPSCs expressed typical pluripotency markers including OCT4, SOX2, and NANOG. Furthermore, differentiation in vivo and in vitro into derivatives of all three germ layers, as well as generation of functional cardiomyocytes, could be demonstrated. Finally, a highly efficient technique for generation of transgenic cyiPSC clones with stable reporter expression in undifferentiated cells as well as differentiated transgenic cyiPSC progeny was developed to enable cell tracking in recipient animals. In conclusion, our data indicate that cyiPSCs represent a valuable cell source for establishment of macaque-based allogeneic and autologous preclinical cell transplantation models for various fields of regenerative medicine.
Authors:
Stephanie Wunderlich; Alexandra Haase; Sylvia Merkert; Jennifer Beier; Kristin Schwanke; Axel Schambach; Silke Glage; Gudrun Göhring; Eliza C Curnow; Ulrich Martin
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cellular reprogramming     Volume:  14     ISSN:  2152-4998     ISO Abbreviation:  Cell Reprogram     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101528176     Medline TA:  Cell Reprogram     Country:  United States    
Other Details:
Languages:  eng     Pagination:  471-84     Citation Subset:  IM    
Affiliation:
1 Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School , 30625 Hannover, Germany .
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