Advances in cell therapies using stem cells/progenitors as a novel approach for neurovascular repair of the diabetic retina.
Advances in cell therapies using stem cells/progenitors as a novel approach for neurovascular repair of the diabetic retina.
复制标题
DOI：
10.1186/s13287-022-03073-x
复制
发表时间：
2022-07-30
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
糖尿病视网膜病变是糖尿病的主要并发症，是导致工作年龄成年人视力下降的主要原因。视网膜神经血管单元完整性的逐渐丧失是该疾病发病机制的核心因素。视网膜缺血和炎症过程驱动相关的病理，如血视网膜屏障破坏，液体积聚，胶质瘤，神经元损失和/或异常的新生血管。目前的治疗选择在某种程度上仅限于疾病的晚期，此时视网膜结构已经因退行性、水肿和增生性病理而受到严重损害。需要针对疾病早期血管退行性和神经退行性阶段的新的预防和介入治疗，以确保避免视力丧失。历史上，糖尿病视网膜病变一直被认为是一种主要的视网膜微血管疾病，临床上根据血管病变的存在和严重程度进行分类。目前已知神经退行性变在发病机制中起重要作用。在临床前模型和糖尿病患者的早期阶段，甚至在临床上明显的糖尿病视网膜病变发病之前，已经记录了神经元的损失。最近的研究表明，一些患者具有主要的神经退行性表型。视网膜色素上皮细胞和脉络膜在疾病发病过程中也受到影响，这些组织也可能需要新的再生治疗。迄今为止，大多数针对糖尿病视网膜病变的干细胞研究都集中在解决血管病变上。本文综述了利用血管活性祖细胞（包括间充质基质/干细胞、脂肪干细胞、CD34+细胞、内皮集落形成细胞和诱导多能干细胞衍生的内皮细胞）修复受损血管系统的临床前和临床研究。可以替代死亡神经元的干细胞，如视网膜祖细胞、多能干细胞衍生的光感受器和神经节细胞以及神经干细胞也进行了讨论。最后，干细胞治疗糖尿病视网膜病变的挑战被考虑。在糖尿病视网膜病变的早期甚至晚期，干细胞疗法在替代死亡细胞方面具有巨大的潜力。然而，由于存在不同的表型，为个体患者选择最合适的干细胞产品将是成功治疗的关键。
Diabetic retinopathy, a major complication of diabetes mellitus, is a leading cause of sigh-loss in working age adults. Progressive loss of integrity of the retinal neurovascular unit is a central element in the disease pathogenesis. Retinal ischemia and inflammatory processes drive interrelated pathologies such as blood retinal barrier disruption, fluid accumulation, gliosis, neuronal loss and/or aberrant neovascularisation. Current treatment options are somewhat limited to late-stages of the disease where there is already significant damage to the retinal architecture arising from degenerative, edematous and proliferative pathology. New preventive and interventional treatments to target early vasodegenerative and neurodegenerative stages of the disease are needed to ensure avoidance of sight-loss. Historically, diabetic retinopathy has been considered a primarily microvascular disease of the retina and clinically it is classified based on the presence and severity of vascular lesions. It is now known that neurodegeneration plays a significant role during the pathogenesis. Loss of neurons has been documented at early stages in pre-clinical models as well as in individuals with diabetes and, in some, even prior to the onset of clinically overt diabetic retinopathy. Recent studies suggest that some patients have a primarily neurodegenerative phenotype. Retinal pigment epithelial cells and the choroid are also affected during the disease pathogenesis and these tissues may also need to be addressed by new regenerative treatments. Most stem cell research for diabetic retinopathy to date has focused on addressing vasculopathy. Pre-clinical and clinical studies aiming to restore damaged vasculature using vasoactive progenitors including mesenchymal stromal/stem cells, adipose stem cells, CD34+ cells, endothelial colony forming cells and induced pluripotent stem cell derived endothelial cells are discussed in this review. Stem cells that could replace dying neurons such as retinal progenitor cells, pluripotent stem cell derived photoreceptors and ganglion cells as well as Müller stem cells are also discussed. Finally, challenges of stem cell therapies relevant to diabetic retinopathy are considered. Stem cell therapies hold great potential to replace dying cells during early and even late stages of diabetic retinopathy. However, due to the presence of different phenotypes, selecting the most suitable stem cell product for individual patients will be crucial for successful treatment.
登录
查看更多内容
影响因子：
40.5
作者：
Antonetti, David A.;Silva, Paolo S.;Stitt, Alan W.
通讯作者：
Stitt, Alan W.
DOI：
10.1056/nejmoa1001288
发表时间：
2010-07-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;ACCORD Eye Study Group;Chew EY;Ambrosius WT;Davis MD;Danis RP;Gangaputra S;Greven CM;Hubbard L;Esser BA;Lovato JF;Perdue LH;Goff DC Jr;Cushman WC;Ginsberg HN;Elam MB;Genuth S;Gerstein HC;Schubart U;Fine LJ
通讯作者：
Fine LJ
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：
3.4
作者：
Bontzos, Georgios;Kabanarou, Stamatina A.;Peto, Tunde
通讯作者：
Peto, Tunde
影响因子：
46.9
作者：
da Cruz, Lyndon;Fynes, Kate;Coffey, Peter J.
通讯作者：
Coffey, Peter J.