Human RPE stem cells grown into polarized RPE monolayers on a polyester matrix are maintained after grafting into rabbit subretinal space.
Human RPE stem cells grown into polarized RPE monolayers on a polyester matrix are maintained after grafting into rabbit subretinal space.
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DOI：
10.1016/j.stemcr.2013.11.005
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发表时间：
2014-01-14
影响因子：
5.9
通讯作者：
Blenkinsop TA
中科院分区：
文献类型：
--
作者：
Stanzel BV;Liu Z;Somboonthanakij S;Wongsawad W;Brinken R;Eter N;Corneo B;Holz FG;Temple S;Stern JH;Blenkinsop TA
视网膜色素上皮(RPE)移植是治疗老年性黄斑变性的一种细胞替代疗法。人胚胎干细胞(HESC)和诱导多能干细胞(IPSC)来源的RPE目前正在转化为临床。我们介绍了成人RPE干细胞(HRPESC)作为替代的RPE来源。生长在聚酯(PET)膜上的成人hRPESC来源的RPE的偏振单分子膜具有近天然的特征。将注射在PET上的RPE单层组织块移植到大眼动物模型兔的视网膜下。4天后，通过光谱域光学相干断层扫描(SD-OCT)和眼底镜检查，在植入物上方观察到视网膜水肿。在第一周，观察到胎儿或成人移植后视网膜萎缩，此后保持稳定。植入后4周的组织学检查证实PET上有连续极化的人RPE单层。综上所述，异种RPE存活下来，并保留了视网膜下腔的特征。这些实验支持成人人RPESC来源的RPE是一种潜在的移植治疗来源。成人hRPESC来源的RPE具有与胎儿hRPE相似的体外特征hRPE单层在兔视网膜下在PET载体上存活4周更好的异种移植存活可能是由于覆盖在hRPE异种移植上的视网膜的hRPE细胞极性萎缩仍然是一个未来的挑战。已经移植了人视网膜色素上皮(HRPE)的极化单层，生长在来自成年hRPE干细胞或兔视网膜下胎儿组织的聚酯膜上。异种RPE存活4周，视网膜下间隙保留细胞极性特征。这些实验支持成人人RPESC来源的RPE是一种潜在的移植治疗来源。
Transplantation of the retinal pigment epithelium (RPE) is being developed as a cell-replacement therapy for age-related macular degeneration. Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are currently translating toward clinic. We introduce the adult human RPE stem cell (hRPESC) as an alternative RPE source. Polarized monolayers of adult hRPESC-derived RPE grown on polyester (PET) membranes had near-native characteristics. Trephined pieces of RPE monolayers on PET were transplanted subretinally in the rabbit, a large-eyed animal model. After 4 days, retinal edema was observed above the implant, detected by spectral domain optical coherence tomography (SD-OCT) and fundoscopy. At 1 week, retinal atrophy overlying the fetal or adult transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. Taken together, the xeno-RPE survived with retained characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies. Adult hRPESC-derived RPE had comparable in vitro characteristics to fetal hRPE hRPE monolayers survived 4 weeks on PET carriers under the rabbit retina Better xenograft survival may be due to the maintained hRPE cell polarity Atrophy of the retina overlaying the hRPE xenograft remains a future challenge Stanzel et al. have transplanted polarized monolayers of human retinal pigment epithelium (hRPE) grown on polyester membranes derived from adult hRPE stem cells or fetal tissue under the rabbit retina. The xeno-RPE survived 4 weeks with retained cell polarity characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies.