Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.
Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia.
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DOI：
10.1080/02713683.2017.1319491
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发表时间：
2017-10
影响因子：
2
通讯作者：
Park SS
中科院分区：
文献类型：
--
作者：
Moisseiev E;Anderson JD;Oltjen S;Goswami M;Zawadzki RJ;Nolta JA;Park SS
来源于在缺氧条件下培养的人间充质干细胞（hMSC）的外泌体含有促进血管生成的蛋白质和生长因子。本研究使用鼠模型研究了玻璃体内施用这些外来体对视网膜缺血的影响。通过将一周龄的雄性C57 BL/6 J小鼠暴露于5天的75%高氧条件下并返回室内空气来诱导氧诱导的视网膜病变（OIR）。在高氧条件化后，将每只小鼠的右眼玻璃体内注射1 μl盐水或来源于hMSC的外泌体，并与在室内空气中饲养的相同年龄的对照小鼠进行比较，而没有玻璃体内注射盐水的OIR。注射后两周，荧光素血管造影（FA）和相位方差光学相干断层扫描血管造影（pvOCTA）用于评估视网膜灌注。视网膜厚度通过OCT确定。视网膜新生血管的程度通过计数视网膜表面上的血管核进行组织学定量。在患有OIR的眼睛中，玻璃体内外泌体治疗部分地保留了体内视网膜血管血流并减少了相关的视网膜变薄; OCT上的视网膜厚度为111.1 ± 7.4μm，盐水组为132.1 ± 11.6μm，p < 0.001。当与盐水处理的眼睛相比时，OIR眼睛中的视网膜新血管形成用外来体处理减少（每个切片7.75 ± 3.68对2.68 ± 1.35个新血管核，p < 0.0001）。没有免疫原性或眼部/全身不良反应与玻璃体内外泌体治疗相关。玻璃体内施用衍生自hMSC的外来体在没有免疫抑制的情况下耐受良好，并且在该鼠模型中降低了视网膜缺血的严重程度。这种吸引人的新型非细胞治疗方法值得进一步探索。
Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 μl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline. Two weeks post-injection, fluorescein angiography (FA) and phase-variance optical coherence tomography angiography (pvOCTA) were used to assess retinal perfusion. Retinal thickness was determined by OCT. The extent of retinal neovascularization was quantitated histologically by counting vascular nuclei on the retinal surface. Among eyes with OIR, intravitreal exosome treatment partially preserved retinal vascular flow in vivo and reduced associated retinal thinning; retinal thickness on OCT was 111.1 ± 7.4μm with saline versus 132.1 ± 11.6μm with exosome, p < 0.001. Retinal neovascularization among OIR eyes was reduced with exosome treatment when compared to saline-treated eyes (7.75 ± 3.68 versus 2.68 ± 1.35 neovascular nuclei per section, p < 0.0001). No immunogenicity or ocular/systemic adverse effect was associated with intravitreal exosome treatment. Intravitreal administration of exosomes derived from hMSCs was well tolerated without immunosuppression and decreased the severity of retinal ischemia in this murine model. This appealing novel non-cellular therapeutic approach warrants further exploration.
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