Rebuilding the Missing Part—A Review on Photoreceptor Transplantation

Santos-Ferreira, Tiago; Borsch, Oliver; Ader, Marius

doi:10.3389/fnsys.2016.00105

Cited by 46 publications

(53 citation statements)

References 88 publications

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“…Several studies have successfully used quantum dot bioconjugates to label stem cells with high efficiency and to track stem cells longitudinally in live rats [117–119]. Though, the transplanted cells may demonstrate integration and evidence of function, more validation studies are required [120–122]. Finally, one of the most difficult challenges will be the precise product characterization of a stem cell, iPSC, or its derived product that meets the standards of regulatory authorities, methods of manufacturing and scale up potential that will meet FDA requirements for human use.…”

Section: Discussionmentioning

confidence: 99%

Recent Advances in Retinal Stem Cell Therapy

2017

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Purpose of review Progress in stem cell research for blinding diseases over the past decade is now being applied to patients with retinal degenerative diseases and soon perhaps, glaucoma. However, the field still has much to learn about the conversion of stem cells into various retinal cell types, and the potential delivery methods that will be required to optimize the clinical efficacy of stem cells delivered into the eye. Recent findings Recent groundbreaking human clinical trials have demonstrated both the opportunities and current limitations of stem cell transplantation for retinal diseases. New progress in developing in vitro retinal organoids, coupled with the maturation of bio-printing technology, and non-invasive high-resolution imaging have created new possibilities for repairing and regenerating the diseased retina and rigorously validating its clinical impact in vivo. Summary While promising progress is being made, meticulous clinical trials with cells derived using good manufacturing practice, novel surgical methods, and improved methods to derive all of the neuronal cell types present in the retina will be indispensable for developing stem cell transplantation as a paradigm shift for the treatment of blinding diseases.

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Section: Discussionmentioning

confidence: 99%

Recent Advances in Retinal Stem Cell Therapy

2017

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“…Prior studies in animal models revealed that photoreceptor transplantation is feasible when the donor cells are at a correct ontogenetic stage at the time of transplantation, corresponding to post mitotic committed photoreceptors (Pearson, 2014;Santos-Ferreira et al, 2017). Initial transplantation studies with photoreceptor precursor cells in different blind rodent models led the investigators to conclude that transplanted cells can survive within the degenerating retina, differentiate into partially mature photoreceptors, form some synaptic connections and that this functional integration could lead to visual improvement (Barber et al, 2013;Eberle et al, 2012;MacLaren et al, 2006;Pearson et al, 2012;Santos-Ferreira et al, 2015;Singh et al, 2013).…”

Section: Therapeutic Strategies For Photoreceptor Degenerative Diseasesmentioning

confidence: 99%

“…Initial transplantation studies with photoreceptor precursor cells in different blind rodent models led the investigators to conclude that transplanted cells can survive within the degenerating retina, differentiate into partially mature photoreceptors, form some synaptic connections and that this functional integration could lead to visual improvement (Barber et al, 2013;Eberle et al, 2012;MacLaren et al, 2006;Pearson et al, 2012;Santos-Ferreira et al, 2015;Singh et al, 2013). However, with the very recent identification of cytoplasmic material exchange between donor and host photoreceptors (see chapter 5.3), former findings assuming donor cell integration in the host retinal circuitry with correct synaptic contacts need to be revisited (Nickerson et al, 2018;Santos-Ferreira et al, 2017).…”

Section: Therapeutic Strategies For Photoreceptor Degenerative Diseasesmentioning

confidence: 99%

Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach

Gagliardi

M’Barek

Goureau

2019

Progress in Retinal and Eye Research

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The human retina fails to regenerate and cell-based therapies offer options for treatment of blinding retinal diseases, such as macular degeneration and retinitis pigmentosa (RP). The last decade has witnessed remarkable advances in generation of retinal cells and retinal tissue from human pluripotent stem cells (PSCs). The development of 3D culture systems allowing generation of human retinal organoids has substantially increased the access to human material for future clinical applications aiming at replacing the lost photoreceptors in retinal degenerative diseases. This review outlines the advances that have been made toward generation and characterization of transplantable photoreceptors from PSCs and summarizes the current status of PSC-based preclinical studies for photoreceptor replacement conducted in animal models. Considering the recent turning point in our understanding of donor photoreceptor integration, this review focuses on the most crucial obstacles that hinder the photoreceptor replacement, discusses the most promising strategies to overcome them in the future, and provides a perspective on the approaching advancement in the application of PSC technology for treatment of photoreceptor degenerative diseases.

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“…Another active area of research on retinal repair is cell replacement to treat mutated, damaged or lost photoreceptors. Over the last two decades, transplantation studies employing a wide variety of donor cell types, such as primary photoreceptors, retinal pigment epithelium (RPE) and retinal progenitor cells (RPCs), have been performed (Santos-Ferreira et al, 2016b). With the exception of RPE (Jin et al, 2019;Mandai et al, 2017), most cell types have shown little efficacy in terms of vision improvement in retinal degeneration mouse models, or clear signs of robust integration into the retina.…”

Section: Extrinsic Therapeutic Strategies For Mammalian Retinal Repairmentioning

confidence: 99%

Awakening the regenerative potential of the mammalian retina

Martin

Poché

2019

Development

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As with all glial cells, the major role of retinal Müller glia (MG) is to provide essential neuronal support. However, the MG of some nonmammalian species have the additional ability to generate new retinal neurons capable of sight restoration. Unfortunately, mammalian MG do not possess this ability. However, if we could understand the reasons why, we may be able to devise strategies to confer regenerative potential. The recent discovery that the Hippo signaling pathway acts as an intrinsic block to mammalian MG proliferation, along with reports of adeno-associated virus (AAV)-based MG reprogramming and functional photoreceptor differentiation, may indicate a watershed moment in the field of mammalian retinal regeneration. However, as researchers delve deeper into the cellular and molecular mechanisms, and further refine MG reprogramming strategies, we should recall past misinterpretations of data in this field and proceed with caution. Here, we provide a summary of these emerging data and a discussion of technical concerns specific to AAV-mediated reprogramming experiments that must be addressed in order for the field to move forward.

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Rebuilding the Missing Part—A Review on Photoreceptor Transplantation

Cited by 46 publications

References 88 publications

Recent Advances in Retinal Stem Cell Therapy

Recent Advances in Retinal Stem Cell Therapy

Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach

Awakening the regenerative potential of the mammalian retina

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