Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
PLoS One. 2010 Feb 15;5(2):e9200. doi: 10.1371/journal.pone.0009200.
Retinitis pigmentosa (RP) is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs) to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS) rat, a well-established animal model for RP.
METHODOLOGY/PRINCIPAL FINDINGS: Animals received syngeneic MSCs (1x10(6) cells) by tail vein at an age before major photoreceptor loss.
both rod and cone photoreceptors were preserved (5-6 cells thick) at the time when control animal has a single layer of photoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells) and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs.
CONCLUSIONS/SIGNIFICANCE: These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with minor discomfort. Therefore, MSCs may prove to be the ideal cell source for auto-cell therapy for retinal degeneration and other ocular vascular diseases.
色素性视网膜炎（RP）的特征是进行性夜盲、视野丧失、血管通透性改变和中心视力丧失。目前，除了基因替代疗法在少数具有特定基因缺陷的患者中显示出前景外，尚无有效的治疗方法。迫切需要开发具有非侵入性干预的通用神经和血管保护作用的治疗方法。在这里，我们探讨了全身给予多能骨髓来源间充质干细胞（MSCs）的潜力，以挽救皇家外科医生学院（RCS）大鼠中的视力和相关血管病理学，这是一种用于 RP 的成熟动物模型。
方法/主要发现：动物在主要光感受器丧失之前通过尾静脉接受同基因 MSC（1x10（6）细胞）。
当对照动物只剩下一层光感受器时，杆状和锥状光感受器都得到了保留（5-6 个细胞厚）；与对照组相比，视觉功能明显得到了保留，这是通过从上丘记录视觉敏锐度和亮度阈值来确定的；病理性血管复合物的数量（与迁移色素上皮细胞相关的异常血管）和通常会发展的血管渗漏面积大大减少；半定量 RT-PCR 分析表明，生长因子的上调，免疫组织化学显示接受 MSC 的动物眼睛内神经营养因子增加。
结论/意义：这些结果强调了 MSCs 在治疗视网膜变性中的潜在应用。这种非侵入性细胞治疗的优势在于：细胞易于分离，可大量扩增用于自体移植；同种异体供体的低免疫原性；比其他干细胞更具争议性；可以在轻微不适的情况下重新给药。因此，MSC 可能被证明是用于治疗视网膜变性和其他眼部血管疾病的自体细胞治疗的理想细胞来源。
