Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.
Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.
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DOI：
10.1016/j.ophtha.2018.04.037
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发表时间：
2018-11
期刊：
影响因子：
13.7
通讯作者：
Bainbridge JWB
中科院分区：
文献类型：
--
作者：
Mehat MS;Sundaram V;Ripamonti C;Robson AG;Smith AJ;Borooah S;Robinson M;Rosenthal AN;Innes W;Weleber RG;Lee RWJ;Crossland M;Rubin GS;Dhillon B;Steel DHW;Anglade E;Lanza RP;Ali RR;Michaelides M;Bainbridge JWB
人胚胎干细胞（hESC）衍生的视网膜色素上皮（RPE）细胞的移植为黄斑变性提供了潜在的益处。以前的试验报告了视力（VA）的改善，但缺乏对治疗区域视网膜结构和功能的详细分析。评价安全性和潜在疗效的I/II期开放标签剂量递增试验（clinicaltrials.gov标识符，NCT 01469832）。12名患有晚期Stargardt病（STGD 1）的参与者，这是儿童和年轻人黄斑变性的最常见原因。视网膜下移植多达200 000个hESC衍生的RPE细胞，并进行13周的全身免疫抑制治疗。主要终点是hESC衍生的RPE细胞施用的安全性和耐受性。我们还研究了移植细胞存活的证据，并使用微视野和光谱域OCT测量视网膜结构和功能。视网膜下色素沉着过度的局灶性区域在所有参与者中以剂量依赖性方式在受体视网膜中发展，并在全身免疫抑制剂撤出后持续存在。我们没有发现不受控制的增殖或炎症反应的证据。4名受试者的最佳矫正视力的边缘改善要么不持续，要么与未经治疗的对侧眼的类似改善相匹配。微视野检查显示12名参与者在12个月时没有获益的证据。在最高剂量下的一个实例中，局部视网膜变薄和色素沉着过度区域的敏感性降低表明可能存在伤害。使用25项国家眼科研究所视觉功能问卷的患者报告的生活质量没有显着变化。视网膜下色素沉着过度与活的移植的hESC衍生的RPE细胞的存活一致，但可能反映在它们不存在时释放的色素。研究结果表明，视网膜结构和功能的空间相关性的详细分析的价值，以适当的灵敏度确定细胞移植的影响，并建议在疾病的早期阶段的干预应谨慎对待。鉴于在疾病的晚期阶段进行性退化的速度缓慢，只有在更长时间的观察之后，才能明显地防止进一步恶化。
Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation.
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Stargardt病：临床特征，分子遗传学，动物模型和治疗选择。
DOI：
10.1136/bjophthalmol-2016-308823
发表时间：
2017-01
期刊：
The British journal of ophthalmology
影响因子：
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作者：
Tanna P;Strauss RW;Fujinami K;Michaelides M
通讯作者：
Michaelides M
DOI：
10.1089/clo.2006.8.189
发表时间：
2006-09-01
期刊：
CLONING AND STEM CELLS
影响因子：
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作者：
Lund, Raymond D.;Wang, Shaomei;Lanza, Robert
通讯作者：
Lanza, Robert
感光体ABC转运蛋白ABCA4在脂质转运和Stargardt黄斑变性中的作用。
DOI：
10.1016/j.bbalip.2009.02.004
发表时间：
2009-07
影响因子：
4.8
作者：
Molday, Robert S.;Zhong, Ming;Quazi, Faraz
通讯作者：
Quazi, Faraz
影响因子：
5.2
作者：
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通讯作者：
Lund, Raymond
影响因子：
1.9
作者：
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通讯作者：
Williams, David S.