c-Kit+ cells isolated from human fetal retinas represent a new population of retinal progenitor cells

Zhou, Pengyi; Peng, Guang-Hua; Xu, Haiwei; Yin, Zheng

doi:10.1242/jcs.169086

Cited by 30 publications

(31 citation statements)

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“…Flow cytometry was used to identify c-kit + /SSEA1 − cells and differentiated cells and was performed as described previously [29, 33, 35]. Briefly, cells cultured in growth medium or differentiation medium were detached using HyQTase (Thermo Fisher Scientific) and collected.…”

Section: Methodsmentioning

confidence: 99%

“…c-kit + cells have been shown to be self-renewing, clonogenic, and multipotent both in vitro and in vivo in hearts, lungs, and other organs [22–24]. Furthermore, c-kit and its ligand, stem cell factor, are both expressed in the CNS and the peripheral nervous system [25–28], as well as in the retinas of humans and mice [29–32]. Purified cells expressing c-kit as a surface marker might have potential future applications for the treatment of retinal degeneration diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Preliminary evidence has indicated that c-kit + cells isolated from humans have potential therapeutic value [29]. However, due to the limitations on combining human cells and a retinal degeneration rat model, the formation of synapses between the grafted cells and recipient retinal cells could not be determined.…”

Section: Introductionmentioning

confidence: 99%

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Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

Chen

et al. 2016

Stem Cell Res Ther

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BackgroundDespite diverse pathogenesis, the common pathological change observed in age-related macular degeneration and in most hereditary retinal degeneration (RD) diseases is photoreceptor loss. Photoreceptor replacement by cell transplantation may be a feasible treatment for RD. The major obstacles to clinical translation of stem cell-based cell therapy in RD remain the difficulty of obtaining sufficient quantities of appropriate and safe donor cells and the poor integration of grafted stem cell-derived photoreceptors into the remaining retinal circuitry.MethodsEye-wall c-kit+/stage-specific embryonic antigen 1 (SSEA1)− cells were isolated via fluorescence-activated cell sorting, and their self-renewal and differentiation potential were detected by immunochemistry and flow cytometry in vitro. After labeling with quantum nanocrystal dots and transplantation into the subretinal space of rd1 RD mice, differentiation and synapse formation by daughter cells of the eye-wall c-kit+/SSEA1− cells were evaluated by immunochemistry and western blotting. Morphological changes of the inner retina of rd1 mice after cell transplantation were demonstrated by immunochemistry. Retinal function of rd1 mice that received cell grafts was tested via flash electroretinograms and the light/dark transition test.ResultsEye-wall c-kit+/SSEA1− cells were self-renewing and clonogenic, and they retained their proliferative potential through more than 20 passages. Additionally, eye-wall c-kit+/SSEA1− cells were capable of differentiating into multiple retinal cell types including photoreceptors, bipolar cells, horizontal cells, amacrine cells, Müller cells, and retinal pigment epithelium cells and of transdifferentiating into smooth muscle cells and endothelial cells in vitro. The levels of synaptophysin and postsynaptic density-95 in the retinas of eye-wall c-kit+/SSEA1− cell-transplanted rd1 mice were significantly increased at 4 weeks post transplantation. The c-kit+/SSEA1− cells were capable of differentiating into functional photoreceptors that formed new synaptic connections with recipient retinas in rd1 mice. Transplantation also partially corrected the abnormalities of inner retina of rd1 mice. At 4 and 8 weeks post transplantation, the rd1 mice that received c-kit+/SSEA1− cells showed significant increases in a-wave and b-wave amplitude and the percentage of time spent in the dark area.ConclusionsGrafted c-kit+/SSEA1− cells restored the retinal function of rd1 mice via regulating neural plasticity and forming new graft-to-host synapses.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0451-8) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

Chen

et al. 2016

Stem Cell Res Ther

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“…Teratoma formation protocol was according to our previous report [38]. Briefly, 100 μl of the cell suspension (1 × 10 6 cells) was subcutaneously implanted into the inguina of SCID mice, regardless of sex.…”

Section: Methodsmentioning

confidence: 99%

Features specific to retinal pigment epithelium cells derived from three-dimensional human embryonic stem cell cultures — a new donor for cell therapy

Zeng

et al. 2016

Oncotarget

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Retinal pigment epithelium (RPE) transplantation is a particularly promising treatment of retinal degenerative diseases affecting RPE-photoreceptor complex. Embryonic stem cells (ESCs) provide an abundant donor source for RPE transplantation. Herein, we studied the time-course characteristics of RPE cells derived from three-dimensional human ESCs cultures (3D-RPE). We showed that 3D-RPE cells possessed morphology, ultrastructure, gene expression profile, and functions of authentic RPE. As differentiation proceeded, 3D-RPE cells could mature gradually with decreasing proliferation but increasing functions. Besides, 3D-RPE cells could form polarized monolayer with functional tight junction and gap junction. When grafted into the subretinal space of Royal College of Surgeons rats, 3D-RPE cells were safe and efficient to rescue retinal degeneration. This study showed that 3D-RPE cells were a new donor for cell therapy of retinal degenerative diseases.

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“…However, for the purpose of discovering the best donors of RPCs as a treatment strategy for RD, the stages at which hRPCs could survive long enough ex vivo and yield maximum the number of target cells still need to be determined. Following transplantation into the subretinal space (SRS) of the Royal College of Surgeons (RCS) rats, the RPCs obtained from human foetal retina during the 12th to 14th week of gestation self-renewed and differentiated into specialized retinal cells for at least three months without forming tumours [30]. Partial prevention of the deterioration of visual acuity was also achieved by grafting RPCs from human foetal (16 weeks) neuroretina into RCS rats [1].…”

Section: Introductionmentioning

confidence: 99%

Progress of stem/progenitor cell-based therapy for retinal degeneration

et al. 2017

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Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

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c-Kit+ cells isolated from human fetal retinas represent a new population of retinal progenitor cells

Abstract: − RPCs exhibit the ability to self-renew and differentiate into retinal cells.

Cited by 30 publications

References 38 publications

Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

Grafted c-kit+/SSEA1− eye-wall progenitor cells delay retinal degeneration in mice by regulating neural plasticity and forming new graft-to-host synapses

Features specific to retinal pigment epithelium cells derived from three-dimensional human embryonic stem cell cultures — a new donor for cell therapy

Progress of stem/progenitor cell-based therapy for retinal degeneration

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