State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
The Second People's Hospital of Foshan, Foshan, 528000, Guangdong, China.
Stem Cell Res Ther. 2021 Mar 10;12(1):168. doi: 10.1186/s13287-021-02180-5.
Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is unclear whether pre-induced hPBMCs can migrate from the injected eye to the contralateral eye for bilateral treatment. We examine the possibility of bilateral cell transplantation from unilateral cell injection.
One hundred and sixty-one 3-month-old retinal degeneration 1 (rd1) mice were divided randomly into 3 groups: an untreated group (n = 45), a control group receiving serum-free Dulbecco's modified Eagle's medium (DMEM) injection into the right subretina (n = 45), and a treatment group receiving injection of pre-induced hPBMCs into the right subretina (n = 71). Both eyes were examined by full-field electroretinogram (ERG), immunofluorescence, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) at 1 and 3 months post-injection.
At both 1 and 3 months post-injection, labeled pre-induced hPBMCs were observed in the retinal inner nuclear layer of the contralateral (left untreated) eye as well as the treated eye as evidenced by immunofluorescence staining for a human antigen. Flow cytometry of fluorescently label cells and qRT-PCR of hPBMCs genes confirmed that transplanted hPBMCs migrated from the treated to the contralateral untreated eye and remained viable for up to 3 months. Further, full-field ERG showed clear light-evoked a and b waves in both treated and untreated eyes at 3 months post-transplantation. Labeled pre-induced hPBMCs were also observed in the contralateral optic nerve but not in the blood circulation, suggesting migration via the optic chiasm.
It may be possible to treat binocular eye diseases by unilateral stem cell injection.
视网膜疾病可能导致失明，因为它们通常会同时影响双眼。将干细胞移植到受影响的眼睛中是治疗某些视网膜疾病的有前途的治疗策略。人外周血单核细胞（hPBMCs）是干细胞的良好来源，但尚不清楚预先诱导的 hPBMCs 是否可以从注射眼迁移到对侧眼以进行双侧治疗。我们研究了从单侧细胞注射进行双侧细胞移植的可能性。
将 161 只 3 个月大的视网膜变性 1 型（rd1）小鼠随机分为 3 组：未治疗组（n=45）、对照组（n=45），对照组右眼接受无血清 DMEM 注射到视网膜下腔，治疗组（n=71）右眼接受预先诱导的 hPBMC 注射。在注射后 1 个月和 3 个月，通过全视野视网膜电图（ERG）、免疫荧光、流式细胞术和定量实时聚合酶链反应（qRT-PCR）检查双眼。
在注射后 1 个月和 3 个月，通过免疫荧光染色检测人类抗原，在对侧（未治疗的左眼）和治疗眼的视网膜内核层观察到标记的预先诱导的 hPBMC。荧光标记细胞的流式细胞术和 hPBMCs 基因的 qRT-PCR 证实，移植的 hPBMC 从治疗眼迁移到未治疗的对侧眼，并在 3 个月内保持存活。此外，在移植后 3 个月，全视野 ERG 在治疗眼和未治疗眼中均显示出清晰的光诱发 a 和 b 波。还观察到标记的预先诱导的 hPBMC 存在于对侧视神经中，但不在血液循环中，表明通过视交叉进行迁移。
通过单侧干细胞注射治疗双眼疾病是可能的。
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