Document Detail


Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature.
MedLine Citation:
PMID:  24163065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The generation of vascular progenitors (VPs) from human induced pluripotent stem cells (hiPSCs) has great potential for treating vascular disorders such as ischemic retinopathies. However, long-term in vivo engraftment of hiPSC-derived VPs into the retina has not yet been reported. This goal may be limited by the low differentiation yield, greater senescence, and poor proliferation of hiPSC-derived vascular cells. To evaluate the potential of hiPSCs for treating ischemic retinopathies, we generated VPs from a repertoire of viral-integrated and nonintegrated fibroblast and cord blood (CB)-derived hiPSC lines and tested their capacity for homing and engrafting into murine retina in an ischemia-reperfusion model.
METHODS AND RESULTS: VPs from human embryonic stem cells and hiPSCs were generated with an optimized vascular differentiation system. Fluorescence-activated cell sorting purification of human embryoid body cells differentially expressing endothelial/pericytic markers identified a CD31(+)CD146(+) VP population with high vascular potency. Episomal CB-induced pluripotent stem cells (iPSCs) generated these VPs with higher efficiencies than fibroblast-iPSC. Moreover, in contrast to fibroblast-iPSC-VPs, CB-iPSC-VPs maintained expression signatures more comparable to human embryonic stem cell VPs, expressed higher levels of immature vascular markers, demonstrated less culture senescence and sensitivity to DNA damage, and possessed fewer transmitted reprogramming errors. Luciferase transgene-marked VPs from human embryonic stem cells, CB-iPSCs, and fibroblast-iPSCs were injected systemically or directly into the vitreous of retinal ischemia-reperfusion-injured adult nonobese diabetic-severe combined immunodeficient mice. Only human embryonic stem cell- and CB-iPSC-derived VPs reliably homed and engrafted into injured retinal capillaries, with incorporation into damaged vessels for up to 45 days.
CONCLUSIONS: VPs generated from CB-iPSCs possessed augmented capacity to home, integrate into, and repair damaged retinal vasculature.
Authors:
Tea Soon Park; Imran Bhutto; Ludovic Zimmerlin; Jeffrey S Huo; Pratik Nagaria; Diana Miller; Abdul Jalil Rufaihah; Connie Talbot; Jack Aguilar; Rhonda Grebe; Carol Merges; Renee Reijo-Pera; Ricardo A Feldman; Feyruz Rassool; John Cooke; Gerard Lutty; Elias T Zambidis
Related Documents :
23074355 - Asymptotic behavior of cell populations described by two-type reducible age-dependent b...
22931165 - The t-box transcription factor brachyury regulates epithelial¿mesenchymal transition in...
24147255 - Role of osteoclasts in regulating hematopoietic stem and progenitor cells.
24599515 - Anti-tcr therapy combined with fingolimod for reversal of diabetic hyperglycemia by β c...
20601035 - Impact of viable cd45 cells infused on lymphocyte subset recovery after unrelated cord ...
22023635 - Current clinical therapies for cartilage repair, their limitation and the role of stem ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-10-25
Journal Detail:
Title:  Circulation     Volume:  129     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-01-21     Completed Date:  2014-03-18     Revised Date:  2014-07-10    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  359-72     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Capillaries / cytology
Cell Aging
DNA Damage
Disease Models, Animal
Embryonic Stem Cells / cytology*
Fetal Blood / cytology*
Fibroblasts / cytology
Graft Survival
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Pluripotent Stem Cells / cytology*
Regeneration
Reperfusion Injury / pathology,  therapy*
Retinal Diseases / pathology,  therapy*
Stem Cell Transplantation / methods*
Transcriptome
Grant Support
ID/Acronym/Agency:
CA60441/CA/NCI NIH HHS; EY01761/EY/NEI NIH HHS; K08 HL077595/HL/NHLBI NIH HHS; R01 CA043318/CA/NCI NIH HHS; R01 EY009357/EY/NEI NIH HHS; R01-EY09357/EY/NEI NIH HHS; R03 HL096220/HL/NHLBI NIH HHS; T32 AI007247/AI/NIAID NIH HHS; U01 HL099775/HL/NHLBI NIH HHS; U01 HL100397/HL/NHLBI NIH HHS; U01HL099775/HL/NHLBI NIH HHS; U01HL100397/HL/NHLBI NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Pathology of Second-Generation Everolimus-Eluting Stents versus First-Generation Sirolimus- and Pacl...
Next Document:  Pro-Inflammatory Endothelial Activation Detected by Molecular Imaging in Obese Non-Human Primates Co...