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Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature.

ABSTRACT: 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.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.VPs generated from CB-iPSCs possessed augmented capacity to home, integrate into, and repair damaged retinal vasculature.

SUBMITTER: Park TS

PROVIDER: S-EPMC4090244 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature.

Park Tea Soon TS Bhutto Imran I Zimmerlin Ludovic L Huo Jeffrey S JS Nagaria Pratik P Miller Diana D Rufaihah Abdul Jalil AJ Talbot Connie C Aguilar Jack J Grebe Rhonda R Merges Carol C Reijo-Pera Renee R Feldman Ricardo A RA Rassool Feyruz F Cooke John J Lutty Gerard G Zambidis Elias T ET

Circulation 20131025 3

<h4>Background</h4>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 retin ...[more]

PMID: 24163065

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Project description:BackgroundThis study aimes to characterize the fundus structural changes in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and the correlation between macular vessel density, retinal nerve fibre layer (RNFL) parameters and visual field sensitivity (VFS) in NAION patients.MethodsA retrospective case control study was performed using 37 eyes with NAION, 30 uninvolved contralateral eyes, and 27 eyes of healthy age-matched subjects. Data on the retinas and choroidal vessel densities and VFS were compared among the three groups.ResultsThe NAION group exhibited significantly lower RNFL thicknesses, lower ganglion cell complexes (GCC), larger global loss volume (GLV) values and focal loss volume (FLV) values when compared with both uninvolved eyes and healthy eyes (p?<?0.01 for all comparisons). The superficial vessel density (SVD) valus (whole, parafovea, superior-hemi and inferior-hemi) were significantly lower in NAION eyes, followed by uninvolved eyes and healthy eyes (p?<?0.01; LSD, p?<?0.05 for all comparisons). The deep vessel density (DVD) values (parafovea, superior-hemi and inferior-hemi) were the lowest by a significant value in NAION eyes, followed by uninvolved eyes and healthy eyes (p?<?0.01; LSD, p?<?0.05 for all comparisons). However, DVD value measurements (whole and fovea) of healthy and uninvolved eyes were not significantly different. The average threshold deviation (TD) was -?11.02?±?3.75?dB for the overall field region, -?6.01?±?2.21?dB for the affected superior field region and?-?9.98?±?3.34?dB for the affected inferior field region in NAION eyes. A statistically significant correlation was found between the RNFL thickness and visual field(VF) loss (r?=?-?0.788, p?<?0.001).ConclusionIn addition to peripapillary vascular changes occurring in NAION eyes, macular vessel density is also involved. Furthermore, NAION-uninvolved eyes exhibited abnormalities compared with healthy eyes. This indicates that vascular changes may occur before changes in retinal thickness at the early stages of NAION.

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Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature.

Publications

Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature.

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