Human Retinal Progenitor Cell Transplantation Preserves Vision

Luo, Jing; Baranov, Petr; Patel, Sheila V.; Ouyang, Hong; Quach, John; Wu, Frances; Qiu, Austin; Luo, Hongrong; Hicks, Caroline; Zeng, Jing; Zhu, Jing; Lu, Jessica R.; Sfeir, Nicole; Wen, Cindy; Zhang, Meixia; Reade, Victoria; Patel, Sara; Sinden, John D.; Sun, Xiaodong; Shaw, Peter X.; Young, Michael J.; Zhang, Kang

doi:10.1074/jbc.m113.513713

Cited by 99 publications

(96 citation statements)

References 33 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the migrated human RPCs failed to express the ganglion cell marker Thy1. It has been previously reported (Luo et al, 2014) that stem cells grafted into the degenerative retina have difficulty differentiating into ganglion and photoreceptor cells in vivo; this finding was consistent with the results from our study.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

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

Zhou

Peng

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 83%

“…After P21, the rod contribution to the mixed b-wave starts declining (Pinilla et al, 2004) and, at P22, changes in photoreceptor nuclei are found (Cuenca et al, 2005). We transplanted cells into the subretina at P21, which is when photoreceptor degeneration begins (Luo et al, 2014). Our experiment showed that grafted c-Kit…”

Section: Discussionmentioning

confidence: 90%

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

Zhou

Peng

et al. 2015

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…In addition, microperimetry can be used to assess retinal function and its changes over time (Scholl, 2004;Sparrow, 2010;Wu, 2014). Studies from multiple groups have demonstrated decreased retinal sensitivity in subjects with early AMD lesions (Wu, 2014) as well as at the retina around GA where autofluorescence changes are seen (Schmitz-Valckenberg et al, 2004).…”

Section: Geographic Atrophymentioning

confidence: 97%

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

Nazari

Zhang

Zhu

et al. 2015

Progress in Retinal and Eye Research

167

133

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular (NV-AMD) or non-neovascular (NNV-AMD). Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD (Geographic Atrophy). In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs (e.g., anti-VEGF) are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells (hESC-RPE) and from induced pluripotent stem cells (iPSC-RPE) has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.

show abstract

“…12 While both of these maintained Ki-67 and pax6 expression, adherent culture can be standardized for scale-up expansion and is less prone to spontaneous differentiation, providing more homogenous populations. We have demonstrated for human 40 RPC that cells propagated as adherent population in 3% oxygen 26 continue to express recoverin, Crx, Nrl, and NeuroD1.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig Retinal Progenitor Cell Allotransplants

Abud

Baranov

Hicks

et al. 2015

Trans. Vis. Sci. Tech.

Self Cite

View full text Add to dashboard Cite

Purpose: The development of photoreceptor replacement therapy for retinal degenerative disorders requires the identification of the optimal cell source and immunosuppressive regimen in a large animal model. Allotransplants are not acutely rejected in swine subretinal space, although it is not known if survival can be improved with immunosuppression. Here we investigated the survival and integration of expanded pig retinal progenitor cells (pRPCs) in normal recipients with and without transient anti-inflammatory suppression.Methods: pRPCs were derived from the neural retina of E60 GFP transgenic pigs, expanded for six passages, characterized, and transplanted into the subretinal space of 12 pigs. Six recipients received a single intravitreal injection of rapamycin and dexamethasone.Results: pRPCs expressed the photoreceptor development genes Sox2, Pax6, Lhx2, Crx, Nrl, and Recoverin in vitro. Transplanted cells were identified in 9 out of 12 recipients 4 weeks after the injection. pRPCs integrated primarily into the photoreceptor inner segment layer and outer nuclear layer with single cells present in the inner nuclear layer. Donor cells remained recoverin-positive and acquired rhodopsin. We did not observe any signs of graft proliferation. The immunosuppression did not affect the survival or distribution of grafts. No macrophage infiltration or loss of retinal structure was observed in either group.Conclusions: Local immunosuppression with rapamycin and dexamethasone does not improve the outcome of pRPC allotransplantation into the subretinal space.Translational Relevance: Survival and integration of pRPC together with the lack of graft proliferation suggests that allogeneic RPC transplantation without transient immunosuppression is a favorable approach for photoreceptor cell replacement.

show abstract

Human Retinal Progenitor Cell Transplantation Preserves Vision

Abstract: Significance: This study provides proof of concept for hRPC transplantation and paves the way for further studies and human trials.

Cited by 99 publications

References 33 publications

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

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

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig Retinal Progenitor Cell Allotransplants

Contact Info

Product

Resources

About