Transplantation of human bone marrow mesenchymal stem cells as a thin subretinal layer ameliorates retinal degeneration in a rat model of retinal dystrophy

Tzameret, Adi; Sher, Ifat; Belkin, Michael; Treves, Abraham J.; Meir, Amilia; Nagler, Arnon; Levkovitch-Verbin, Hani; Barshack, Iris; Rosner, Mordechai; Rotenstreich, Ygal

doi:10.1016/j.exer.2013.10.023

Cited by 121 publications

(141 citation statements)

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“…However, in our study the proportion of cells expressing rhodopsin (4.0±0.3%) was lower than the proportion reported in the study by Coles et al (34.5±9.1%); furthermore, we found that more cells differentiated into glial cells (66.7±5.8%) than has been previously reported (19.7±10.6%) (Coles et al, 2004). The transplantation of stem cells into the subretina of rats or mice that are afflicted by retinal degeneration has been demonstrated to produce a neuroprotective effect (Tian et al, 2011;Tzameret et al, 2014). In our study, we found that transplantation of c-Kit…”

Section: Discussioncontrasting

confidence: 55%

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

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Section: Discussioncontrasting

confidence: 55%

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

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“…There have been similar recent reports of proinflammatory vitreous clumping of MSCs injected intravitreally 47 as well as thick epiretinal membrane formation following MSC administration in humans. 48 These adverse effects may also be due in part to the inconsistency in MSC isolation and preparation.…”

Section: Eyesupporting

confidence: 49%

Protecting retinal ganglion cells

Khatib

Martin

2017

Eye

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Retinal ganglion cell degeneration underlies several conditions which give rise to significant visual compromise, including glaucoma, hereditary optic neuropathies, ischaemic optic neuropathies, and demyelinating disease. In this review, we discuss the emerging strategies for neuroprotection specifically in the context of glaucoma, including pharmacological neuroprotection, mesenchymal stem cells, and gene therapy approaches. We highlight potential pitfalls that need to be considered when developing these strategies and outline future directions, including the prospects for clinical trials.

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“…20 Such events were clearly observed under OCT by the absence of a subretinal bleb at a host site where QT was observed under fcSLO ( Figure 2b; n = 3, recipients: 4-6). Notably, ophthalmoscopy could not detect this form of misplacement, though graft injected into the choroid could also not be resolved from vasculature under OCTcombination of the two modalities (OCT and fcSLO) were required to determine this misplacement.…”

Section: Detection Of Graft Misplacement and Traumamentioning

confidence: 95%

Bimodal in vivo imaging provides early assessment of stem-cell-based photoreceptor engraftment

Laver

Metcalfe

Szczygiel

et al. 2015

Eye

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Purpose Subretinal transplantation of stem-cell-derived photoreceptor precursor cells (PPCs) is a promising and innovative approach to treating a range of blinding diseases. However, common barriers to efficient preclinical transplantation comes in the form of suboptimal graft architecture, limited graft survival, and immune-rejection, each of which cannot be assessed using conventional in vivo imaging (ie, rodent ophthalmoscopy). With the majority of PPCs reported to die within the first few weeks after transplantation, understanding the mechanisms of graft failure, and ultimately devising preventative methods, currently relies on lengthy end point histology.To address these limitations, we hypothesized that combining two imaging modalities, optical coherence tomography (OCT) and fluorescence confocal scanning laser ophthalmoscopy (fcSLO), could provide a more rapid and comprehensive view of PPC engraftment. Methods Human ESC-derived PPCs were transplanted into 15 retinal dystrophic rats that underwent bimodal imaging at 0, 8, and 15 days posttransplant. Results Bimodal imaging provided serial detection of graft: placement, architecture, and survival; each undetectable under ophthalmoscopy. Bimodal imaging determined graft placement to be either: subretinal (n = 7), choroidal (n = 4), or vitreal (n = 4) indicating neural retinal perforation. Graft architecture was highly variable at the time of transplantation, with notable redistribution over time, while complete, or near complete, graft loss was observed in the majority of recipients after day 8. Of particular importance was detection of vitreal aggregates overlying the graft-possibly an indicator of host-site inflammation and rejection. Conclusion Early real-time feedback of engraftment has the potential to greatly increase efficiency of preclinical trials in cell-based retinal therapeutics.

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Transplantation of human bone marrow mesenchymal stem cells as a thin subretinal layer ameliorates retinal degeneration in a rat model of retinal dystrophy

Cited by 121 publications

References 42 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

Protecting retinal ganglion cells

Bimodal in vivo imaging provides early assessment of stem-cell-based photoreceptor engraftment

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