Preclinical Evaluation and Optimization of a Cell Therapy Using Human Cord Blood-Derived Endothelial Colony-Forming Cells for Ischemic Retinopathies.
Preclinical Evaluation and Optimization of a Cell Therapy Using Human Cord Blood-Derived Endothelial Colony-Forming Cells for Ischemic Retinopathies.
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DOI：
10.1002/sctm.17-0187
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发表时间：
2018-01
影响因子：
6
通讯作者：
Medina RJ
中科院分区：
文献类型：
--
作者：
Reid E;Guduric-Fuchs J;O'Neill CL;Allen LD;Chambers SEJ;Stitt AW;Medina RJ
使用内皮祖细胞的细胞疗法有望用于缺血性视网膜病变的血管修复。使用定义明确的人脐带血来源的内皮祖细胞亚群，称为内皮集落形成细胞(ECFC)，我们评估了进一步开发这种针对缺血视网膜的细胞疗法的基本要求，包括剂量反应、传递途径和毒性。首先，为了评估与细胞剂量相关的治疗效果，将ECFCs注入氧诱导的视网膜病变小鼠的玻璃体中。通过血管造影和组织学检查，我们发现低剂量(1×103)ECFCs玻璃体腔内注射与高剂量(1×104、1×105)细胞注射同样有效地促进血管修复。其次，颈总动脉注射作为一种替代的全身给药途径进行了测试。颈动脉内注射ECFC可提供与使用相同ECFC剂量(1×105)的玻璃体内注射相当的疗效，尽管全身注射后视网膜血管中观察到的人类细胞较少。第三，通过向健康成年小鼠玻璃体内注射ECFCs来评价细胞免疫原性。对小鼠眼组织的评估确定了玻璃体中的注射细胞，同时证明了宿主视网膜的完整性。此外，ECFC没有侵入视网膜，而是留在玻璃体中，在那里它们最终在交付后3天内经历细胞死亡，没有引起炎症反应。在ECFC接种3天后，在健康的小鼠视网膜中没有发现人类特有的Alu序列。这些发现为ECFCs作为治疗缺血性视网膜病变的有效细胞产品的发展提供了支持的临床前证据。干细胞转化医学2018；7：59-67
Cell therapy using endothelial progenitors holds promise for vascular repair in ischemic retinopathies. Using a well‐defined subpopulation of human cord blood‐derived endothelial progenitors known as endothelial colony‐forming cells (ECFCs), we have evaluated essential requirements for further development of this cell therapy targeting the ischemic retina, including dose response, delivery route, and toxicity. First, to evaluate therapeutic efficacy relating to cell dose, ECFCs were injected into the vitreous of mice with oxygen‐induced retinopathy. Using angiography and histology, we found that intravitreal delivery of low dose (1 × 103) ECFCs was as effective as higher cell doses (1 × 104, 1 × 105) in promoting vascular repair. Second, injection into the common carotid artery was tested as an alternative, systemic delivery route. Intracarotid ECFC delivery conferred therapeutic benefit which was comparable to intravitreal delivery using the same ECFC dose (1 × 105), although there were fewer human cells observed in the retinal vasculature following systemic delivery. Third, cell immunogenicity was evaluated by injecting ECFCs into the vitreous of healthy adult mice. Assessment of murine ocular tissues identified injected cells in the vitreous, while demonstrating integrity of the host retina. In addition, ECFCs did not invade into the retina, but remained in the vitreous, where they eventually underwent cell death within 3 days of delivery without evoking an inflammatory response. Human specific Alu sequences were not found in healthy mouse retinas after 3 days of ECFC delivery. These findings provide supportive preclinical evidence for the development of ECFCs as an efficacious cell product for ischemic retinopathies. stem cells translational medicine 2018;7:59–67
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影响因子：
17.8
作者：
Jones MK;Lu B;Girman S;Wang S
通讯作者：
Wang S
影响因子：
6
作者：
Medina RJ;Barber CL;Sabatier F;Dignat-George F;Melero-Martin JM;Khosrotehrani K;Ohneda O;Randi AM;Chan JKY;Yamaguchi T;Van Hinsbergh VWM;Yoder MC;Stitt AW
通讯作者：
Stitt AW
影响因子：
7.7
作者：
Caballero, Sergio;Sengupta, Nilanjana;Grant, Maria B.
通讯作者：
Grant, Maria B.
影响因子：
3.9
作者：
Falavarjani, K. Ghasemi;Nguyen, Q. D.
通讯作者：
Nguyen, Q. D.
DOI：
10.1073/pnas.1405388111
发表时间：
2014-07-15
影响因子：
11.1
作者：
Lin, Ruei-Zeng;Moreno-Luna, Rafael;Melero-Martin, Juan M.
通讯作者：
Melero-Martin, Juan M.