Stem cell‐based treatment in geographic atrophy: promises and pitfalls

Kvanta, Anders; Grudzińska, M

doi:10.1111/aos.12185

Cited by 20 publications

(23 citation statements)

References 57 publications

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“…Hematopoietic SC (HSC) were identified in 1961, and their ability to migrate and differentiate into multiple cell types was documented [8][9][10] . SC transplants may be xenogenic (from another species), allogenic (from another individual) or autograft (from the same individual) [2,4] . The immunological ocular privilege provides, both allogenic and xenogenic intraocular grafts, a long term survival, when compared with similar grafts [11] .…”

Section: Stem Cells and Cell Replacementmentioning

confidence: 99%

“…The immunological ocular privilege provides, both allogenic and xenogenic intraocular grafts, a long term survival, when compared with similar grafts [11] . The human embryonic (hESC) and the induced pluripotent (iPSC) consist, at this moment, as the major forms of retinal SC therapy [4] . The hESC are derived from blastocysts, left from procedures of "in vitro" fertilization.…”

Section: Stem Cells and Cell Replacementmentioning

confidence: 99%

“…Takahashi and Yamanaka, reprogrammed peripheral normal adult fibroblasts and lymphoblasts, into human iPSC [1,12] . Both hESC and iPSC have similar characteristics and potential for retinal differentiation, with morphological similarities to the RPE, bringing a total new horizon for retinal degenerations, producing RPE in possibly unlimited amounts [1,4,7] . Human iPSC are normal fibroblasts or lymphoblasts, and can be obtained from any adult individual, including the patient itself [1,4] .…”

Section: Stem Cells and Cell Replacementmentioning

confidence: 99%

“…It provides both metabolic and functional support of photoreceptors, replenishing bleached photopigments that, after a photon is absorbed, initiates the phototransduction, through an active participation from the RPE and the photoreceptors [1,2] . The RPE forms with the photoreceptors a functional unit, and its optimal functioning is critical to sight [1,4] . Loss of the integrity of this unit, promotes apoptosis or degeneration of the photoreceptors [1,2] .…”

Section: Introductionmentioning

confidence: 99%

“…Loss of the integrity of this unit, promotes apoptosis or degeneration of the photoreceptors [1,2] . Retinal degeneration occurs in several forms, such as age related macular degeneration (AMD), Stargadt's macular dystrophy and retinitis pigmentosa (RP) [2,4,5] . The AMD has a multifactorial pathophysiology, which results in photoreceptors degeneration in the macula.…”

Section: Introductionmentioning

confidence: 99%

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Stem cell therapy for retinal diseases

Garcia

Mendonça

Brant

et al. 2015

WJSC

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In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt's dystrophy, and patients with geographic atrophy, providing good outcomes. This study's intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients' vision, and, finally, approaching future directions and challenges for the treatment of several conditions.

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Section: Stem Cells and Cell Replacementmentioning

confidence: 99%

Section: Stem Cells and Cell Replacementmentioning

confidence: 99%

Section: Stem Cells and Cell Replacementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stem cell therapy for retinal diseases

Garcia

Mendonça

Brant

et al. 2015

WJSC

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Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration

Cao

Murat

et al. 2015

Stem Cells

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Retinal pigment epithelium (RPE) cells perform many functions crucial for retinal preservation and vision. RPE cell dysfunction results in various retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). Currently, there are no effective treatments for retinal degeneration except for a small percentage of individuals with exudative AMD. Cell therapies targeting RPE cells are being developed in the clinic for the treatment of retinal degeneration. Subretinal injection of human umbilical tissue-derived cells (hUTC) in the Royal College of Surgeons (RCS) rat model of retinal degeneration was shown to preserve photoreceptors and visual function. However, the precise mechanism remains unclear. Here, we demonstrate that hUTC rescue phagocytic dysfunction in RCS RPE cells in vitro. hUTC secrete receptor tyrosine kinase (RTK) ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as opsonizing bridge molecules milk-fat-globule-epidermal growth factor 8 (MFG-E8), growth arrest-specific 6 (Gas6), thrombospondin (TSP)-1, and TSP-2. The effect of hUTC on phagocytosis rescue in vitro is mimicked by recombinant human proteins of these factors and is abolished by siRNAtargeted gene silencing in hUTC. The bridge molecules secreted from hUTC bind to the photoreceptor outer segments and facilitate their ingestion by the RPE. This study elucidates novel cellular mechanisms for the repair of RPE function in retinal degeneration through RTK ligands and bridge molecules, and demonstrates the potential of using hUTC for the treatment of retinal degenerative diseases. STEM CELLS 2016;34:367-379 SIGNIFICANCE STATEMENTRetinal degeneration is a leading cause of blindness. There is currently no effective treatment. Retinal pigment epithelium (RPE) play a pivotal role in retinal preservation. The phagocytic function of the RPE is crucial for the integrity of the light-sensing photoreceptors, thus vision. We previously reported that subretinal injection of human umbilical tissue-derived cells (hUTC) in a rodent model of retinal degeneration preserved photoreceptors and vision with an unknown mechanism. Here, we report that hUTC can rescue RPE phagocytic dysfunction through the release of receptor tyrosine kinase ligands and bridge molecules. This study identifies novel mechanisms of a cell-based therapy for correcting the RPE dysfunction in retinal degeneration, suggesting that hUTC may provide utility in treating patients with retinal degenerative diseases, such as AMD and retinitis pigmentosa.

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Treatment of Geographic Atrophy: What’s on the Horizon?

Thorell

Rosenfeld

2014

Curr Ophthalmol Rep

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Currently, there is no treatment to stop the progression of geographic atrophy, the advanced form of non-exudative (dry) age-related macular degeneration. Several promising therapies are being investigated in clinical trials such as antioxidants, neuroprotection agents, complement inhibitors, vascular enhancers, visual cycle modulators, and stem cell therapies. This review discusses the possible treatments that may potentially be available in the future to prevent disease progression.

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Stem cell‐based treatment in geographic atrophy: promises and pitfalls

Cited by 20 publications

References 57 publications

Stem cell therapy for retinal diseases

Stem cell therapy for retinal diseases

Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration

Treatment of Geographic Atrophy: What’s on the Horizon?

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