Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

Schwartz, Steven D.; Regillo, Carl D.; Lam, Byron L.; Eliott, Dean; Rosenfeld, Philip J.; Gregori, Ninel Z.; Hubschman, Jean‐Pierre; Davis, Janet L.; Heilwell, Gad; Spirn, Marc J.; Maguire, Joseph I.; Bateman, Jane; Ostrick, Rosaleen; Morris, Debra; Vincent, Matthew; Anglade, Eddy; Priore, Lucian V. Del; Lanza, Robert

doi:10.1016/s0140-6736(14)61376-3

Cited by 1,109 publications

(936 citation statements)

References 31 publications

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“…Although the discussion here has focused on AMD, interventions aimed at bisretinoids would also be applicable to less common diseases such as STGD1. In the latter early-onset form of macular degeneration, gene therapy promises to correct the accelerated bisretinoid deposition that is a consequence of most ABCA4 mutations (73,74), whereas cell-based therapies aim to replace the damaged RPE (75).…”

Section: Other Considerationsmentioning

confidence: 99%

Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics

Sparrow

2016

Proc. Natl. Acad. Sci. U.S.A.

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Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.age-related macular degeneration | vitamin A-aldehyde adducts | bisretinoids | retinal pigment epithelium | photoreceptor cells Age-related macular degeneration (AMD) is a complex disorder that is predicted to have a growing impact on elderly populations. Although the cause of central vision loss in AMD is the progressive impairment of photoreceptor cells, the disease is generally thought to begin with dysfunctioning of retinal pigment epithelium (RPE) and adverse changes in subjacent Bruch's membrane (1, 2). The early stage of the disease is typically marked by extracellular accumulations (drusen) between RPE and Bruch's membrane. Progression to advanced disease is defined by delineated areas devoid of RPE and photoreceptor cell loss (atrophic AMD) and/or abnormal growth of blood vessels underneath RPE or within the subretinal space (neovascular AMD). AMD Risk FactorsAMD susceptibility is influenced by multiple factors of both genetic and environmental origin. Predisposing genetic factors account for 71% of the variation in disease risk among individuals (3). Currently, 52 independently associated genetic variants at 34 loci are known to account for ∼50% of AMD heritability (4). The genes implicated by these variants belong to multiple systems some of which are associated with the complement pathway, lipid metabolism, and maintenance of extracellular matrix (5, 6). Nevertheless, many individuals carrying risk variants do not develop AMD.Two loci, CFH (complement factor H; 1q31) and ARMS2/HTRA1 (age-related maculopathy susceptibility 2/high-temperature requirement factor A1; 10q26), make the greatest contribution to AMD risk. Variants at the ARMS2/HTRA1 and CFH loci significantly increase risk for progression to both the atrophic and neovascular forms of AMD, although the magnitude of the association of the ARMS2/HTRA1 risk allele is somewhat greater for the neovascular phenotype of late AMD, whereas CFH risk variants favor progression toward geogr...

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Section: Other Considerationsmentioning

confidence: 99%

Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics

Sparrow

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Une étude menée par R.P. Lanza, a permis de montrer la bonne tolérance à l'implantation sous-rétinienne de CSE humaines différenciées, chez neuf sujets [22] sans signes de prolifération incontrôlée des cellules injectées. …”

Section: Progéniteurs Facultatifs Dans Le Pancréas Adulteunclassified

La thérapie cellulaire du diabète

Lysy

2016

Med Sci (Paris)

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> La poss ibilité de remplacer des cellules β déficientes par de nouvelles cellules insulinosécrétantes chez le patient diabétique est démontrée par le succès de la transplantation d'îlots pancréatiques. Le manque de donneurs cadavériques a stimulé la recherche de sources alternatives de cellules β dont le palmarès est dominé par les cellules souches pluripotentes humaines pouvant acquérir des caractéristiques quasiment identiques à celles des cellules β et rétablir l'équilibre glycémique de souris diabétiques. Néanmoins, elles comportent un risque carcinogénique actuellement inévitable. Le pancréas adulte héberge des compartiments cellulaires aux capacités de transdifférenciation établies pouvant être exploitées pharmacologiquement in situ ou via des phases d'expansion en culture. Cette revue s'intéresse aux nouveaux développements concernant la thérapie cellulaire du diabète. < vie permettent de prévenir 60 % des DT2, il n'y a, à ce jour, aucune straté-gie de prévention du DT1 et les traitements actuels ne permettent pas d'atteindre les objectifs thérapeutiques tels que révélés par le dosage de l'hémoglobine glyquée (ou glycatée) (HbA1 C ) 2 [1]. Le DT1 est donc la cible des stratégies développées pour le remplacement des cellules β qui ont vu le jour en 1966 à Minneapolis avec la première greffe de pancréas humain combinée à une greffe de rein [2]. Après plus de 47 000 greffes d'organe (pancréas associé au rein ou pancréas seul), la technique a été nettement raffinée. Elle permet actuellement une survie des greffons d'environ 85 % à 1 an post-chirurgie [3], ce qui en fait une option thérapeutique pour des patients diabétiques en insuffisance rénale [4]. Cette technique n'est malgré tout pas généralisable étant donnés les degrés de morbidité et de mortalité associés au geste chirurgical (75 % de survie à 10 ans), la nécessité d'une immunosuppression à vie, et le manque de donneurs d'organe. Ces difficultés ont stimulé la recherche pour une thérapie cellulaire du diabète fondée sur des sources cellulaires variées comme les îlots pancréatiques 3 , les cellules souches pluripotentes ou les cellules somatiques adultes du pancréas. Transplantation des îlots pancréatiquesLa transplantation des îlots de Langerhans du pancréas humain s'est développée dans les années 1970, comme une alternative moins invasive à la greffe de pancréas entier. Cette technique a bénéficié de la 2 L'hémoglobine glyquée est une forme d'hémoglobine ayant subi une glycation, c'est-à-dire une addition non enzymatique de sucre sur la protéine. C'est un marqueur de la glycémie. 3 Les îlots pancréatiques, ou îlots de Langerhans sont formés de cellules endocrines capables de synthéti-ser l'insuline, le glucagon, la somatostatine et le polypeptide pancréatique.

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“…Human ESC (hESC) were the first pluripotent stem cell source [35], and results of first clinical studies using hESC for regenerative repair in the eye have recently been reported [36,37].…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

“…In a follow-up period of 22 months, patients receiving hESC-derived retinal pigment epithelial cells for therapy showed no unwanted cell proliferation of the graft or severe adverse events. Fifty-five percent of the eyes receiving transplantation of hESC-derived retinal pigment epithelial cells showed improved visual acuity, whereas the untreated fellow eyes did not [37]. Recently, a Japanese woman received autologous hiPSC-derived retinal pigment epithelial cells as therapy for her visual impairment [73].…”

Section: Current State Of Clinical Application With Pluripotent Stem mentioning

confidence: 99%

Engineering Cardiovascular Regeneration

et al. 2015

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The human heart has very limited regenerative capacity, making the loss of heart muscle tissue during myocardial infarction essentially irreversible. Regenerative medicine aims at promoting the formation of new functional heart muscle in an injured heart, either by stimulating myocyte proliferation, formation of myocytes from preexisting stem cells, direct reprogramming of fibroblasts into myocytes, or adding new muscle tissue from exogenous stem cell sources. Recent advances in stem cell research make these goals more realistic. This review provides a short overview about different approaches for cardiovascular regeneration, stem cell sources, and modes of application, focusing on current cardiac tissue engineering techniques and their way towards clinical application.

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Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies

Cited by 1,109 publications

References 31 publications

Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics

Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics

La thérapie cellulaire du diabète

Engineering Cardiovascular Regeneration

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