Surgical Approaches for Cell Therapeutics Delivery to the Retinal Pigment Epithelium and Retina

Stanzel, Boris V.; Ader, Marius; Liu, Zengping; Amaral, Juan; Aguirre, Luis Ignacio Reyes; Rickmann, Annekatrin; Barathi, Veluchamy A; Tan, Gavin Siew Wei; Degreif, Andrea; Al-Nawaiseh, Sami; Szurman, Peter

doi:10.1007/978-3-030-28471-8_6

Cited by 17 publications

(23 citation statements)

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“…A second limitation of this study is that it is a xenotransplant. This possibly limits the subretinal integration of hRPESC-RPE due to both systemic and local immune reactions (Stanzel et al, 2014(Stanzel et al, , 2019. Similar to our observation of reduced ONL underneath the xenografted RPE monolayer, Diniz et al also observed progressive reductions in athymic nude rats receiving hESC-RPE transplants, suggesting a variant of a graft-versus-host reaction (Diniz et al, 2013).…”

Section: Discussionsupporting

confidence: 86%

“…Sirolimus was used orally with a loading dose of 2 mg, followed by a 1 mg daily dose. Tetracycline antibiotics (doxycycline and minocycline) were administered orally in doses of 7.5 mg kg À1 body weight (BW), twice a day as previously described (Sharma et al, 2019;Stanzel et al, 2019). All animals were monitored closely to ensure that the immunosuppression had no effect on the general well-being of the animals.…”

Section: Immunosuppressionmentioning

confidence: 99%

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Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

et al. 2021

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Summary Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month. The present study placed hRPESC-RPE monolayers under the macula of a non-human primate model for 3 months. The transplant was able to recover in vivo and maintained healthy photoreceptors. Importantly, there was no evidence that subretinally transplanted monolayers underwent an epithelial-mesenchymal transition. Neither gliosis in adjacent retina nor epiretinal membranes were observed. These findings suggest that hRPESC-RPE monolayers are safe and may be a useful source for RPE cell replacement therapy.

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Section: Discussionsupporting

confidence: 86%

Section: Immunosuppressionmentioning

confidence: 99%

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

et al. 2021

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“…Consequently, studies might have under-or overestimated their data which affects our meta-analysis [67]. Moreover, translational value to humans might be low because preclinical in vivo studies are generally not using sufficient animal numbers due to high costs [68,69]. Nonetheless, underpowered studies are included in this systematic review as well, because we wanted to give a full overview of the preclinical RPE transplantation field.…”

Section: Methodological Limitationsmentioning

confidence: 99%

“…Intravitreal injections are hardly used since the transplanted RPE cells have to pass the retinal layers to reach the host's RPE layer. Most recently it was postulated that RPE transplantation by means of a cell suspension injection might not be the most optimal procedure [69]. Dissociated cells that are injected into the subretinal space need to integrate into the host's RPE layer and form a strong and new functional epithelial layer.…”

Section: Delivery Methods: Cell Suspensions or Monolayers?mentioning

confidence: 99%

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Koster

Wever

Wagstaff

et al. 2020

IJMS

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The retinal pigment epithelium (RPE) and the adjacent light-sensitive photoreceptors form a single functional unit lining the back of the eye. Both cell layers are essential for normal vision. RPE degeneration is usually followed by photoreceptor degeneration and vice versa. There are currently almost no effective therapies available for RPE disorders such as Stargardt disease, specific types of retinitis pigmentosa, and age-related macular degeneration. RPE replacement for these disorders, especially in later stages of the disease, may be one of the most promising future therapies. There is, however, no consensus regarding the optimal RPE source, delivery strategy, or the optimal experimental host in which to test RPE replacement therapy. Multiple RPE sources, delivery methods, and recipient animal models have been investigated, with variable results. So far, a systematic evaluation of the (variables influencing) efficacy of experimental RPE replacement parameters is lacking. Here we investigate the effect of RPE transplantation on vision and vision-based behavior in animal models of retinal degenerated diseases. In addition, we aim to explore the effect of RPE source used for transplantation, the method of intervention, and the animal model which is used. Methods: In this study, we systematically identified all publications concerning transplantation of RPE in experimental animal models targeting the improvement of vision (e.g., outcome measurements related to the morphology or function of the eye). A variety of characteristics, such as species, gender, and age of the animals but also cell type, number of cells, and other intervention characteristics were extracted from all studies. A risk of bias analysis was performed as well. Subsequently, all references describing one of the following outcomes were analyzed in depth in this systematic review: a-, b-, and c-wave amplitudes, vision-based, thickness analyses based on optical coherence tomography (OCT) data, and transplant survival based on scanning laser ophthalmoscopy (SLO) data. Meta-analyses were performed on the a-and b-wave amplitudes from electroretinography (ERG) data as well as data from vision-based behavioral assays. Results: original research articles met the inclusion criteria after two screening rounds. Overall, most studies were categorized as unclear regarding the risk of bias, because many experimental details were poorly reported. Twenty-three studies reporting one or more of the outcome measures of interest were eligible for either descriptive (thickness analyses based on OCT data; n = 2) or meta-analyses. RPE transplantation significantly increased ERG a-wave Int.(Hedges' g 1.181 (0.471-1.892), n = 6) and b-wave (Hedges' g 1.734 (1.295-2.172), n = 42) amplitudes and improved vision-based behavior (Hedges' g 1.018 (0.826-1.209), n = 96). Subgroup analyses revealed a significantly increased effect of the use of young and adolescent animals compared to adult animals. Moreover, transplanting more cells (in the range of 10 5 versus in the range o...

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“…4 und 5), insbesondere von submakulären RPE-Zell-Sheets (RPE: retinales Pigmentepithel) auf Trägermatrix [12]. Dieser derzeit hoffnungsvolle Ansatz zur Behandlung der exsudativen ebenso wie der trockenen AMD steht wenige Jahre vor der klinisch breiten Einführung und wird erheblich von der iOCT profitieren [13].…”

Section: Mehrwert Der Ioct Bei Sonderindikationenunclassified

Stellenwert der intraoperativen optischen Kohärenztomografie in der Netzhautchirurgie. Teil 2: contra

Szurman

2020

Klin Monbl Augenheilkd

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ZusammenfassungEine der kontroversesten Diskussionen in der Netzhautchirurgie wird derzeit über den Stellenwert der intraoperativen optischen Kohärenztomografie (iOCT) geführt. Hintergrund ist der Wunsch, den 2-dimensionalen Fundusblick des Operateurs mit der geschichteten Tiefeninformation der OCT zu kombinieren, um eine Art 4-dimensionale „Augmented Reality“ (3-D plus Veränderung über die Zeit) zu erreichen. Dies soll feine Strukturen, die dem Blick des Operateurs bisher verborgen sind, sichtbar machen. Deshalb erscheint die Netzhautchirurgie prädestiniert für den Einsatz einer iOCT zu sein. Die große Hoffnung liegt darin, dass ein dynamisches Live-3-D-Bild mit Echtzeit-Feedback dem Operateur zusätzliche Informationen liefert und die Sicherheit verbessert. So faszinierend die iOCT-Technologie auf den ersten Blick ist, so enttäuscht sie doch im klinischen Alltag, gerade in der Makulachirurgie. Sie liefert nur selten Informationen, die ohne iOCT nicht erzielbar wären oder durch präoperative Diagnostik nicht in wesentlich besserer Qualität vorlägen. Hoffnungsvoll sind einige Sonderindikationen, die insbesondere die subretinale Chirurgie betreffen.

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Surgical Approaches for Cell Therapeutics Delivery to the Retinal Pigment Epithelium and Retina

Cited by 17 publications

References 50 publications

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression

A Systematic Review on Transplantation Studies of the Retinal Pigment Epithelium in Animal Models

Stellenwert der intraoperativen optischen Kohärenztomografie in der Netzhautchirurgie. Teil 2: contra

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