State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
Cytotherapy. 2013 Nov;15(11):1416-25. doi: 10.1016/j.jcyt.2013.05.025.
Recent advances in stem cell research have raised the possibility of stem cells repairing or replacing retinal photoreceptor cells that are either dysfunctional or lost in many retinal diseases. Various types of stem cells have been used to replace retinal photoreceptor cells. Recently, peripheral blood stem cells, a small proportion of pluripotent stem cells, have been reported to mainly exist in the peripheral blood mononuclear cells (PBMCs).
In this study, the effects of pre-induced adult human PBMCs (hPBMCs) on the degenerative retinas of rd1 mice were investigated. Freshly isolated adult hPBMCs were pre-induced with the use of the conditioned medium of rat retinas for 4 days and were then labeled with chloromethyl-benzamidodialkylcarbocyanine (CM-DiI) and then transplanted into the subretinal space of the right eye of rd1 mice through a trans-scleral approach. The right eyes were collected 30 days after transplantation. The survival and migration of the transplanted cells in host retinas were investigated by whole-mount retinas, retinal frozen sections and immunofluorescent staining.
After subretinal transplantation, pre-induced hPBMCs were able to survive and widely migrate into the retinas of rd1 mice. A few CM-DiI-labeled cells migrated into the inner nuclear layer and the retinal ganglion cell layer. Some transplanted cells in the subretinal space of rd1 host mice expressed the human photoreceptor-specific marker rhodopsin.
This study suggests that pre-induced hPBMCs may be a potential cell source of cell replacement therapy for retinal degenerative diseases.
最近干细胞研究的进展提出了这样一种可能性，即干细胞可以修复或替代在许多视网膜疾病中功能失调或丧失的视网膜光感受器细胞。已经使用各种类型的干细胞来替代视网膜光感受器细胞。最近，有报道称外周血干细胞（一种少量的多能干细胞）主要存在于外周血单个核细胞（PBMC）中。
在这项研究中，研究了预诱导的成人人类 PBMC（hPBMC）对 rd1 小鼠退行性视网膜的影响。使用大鼠视网膜的条件培养基将新鲜分离的成人 hPBMC 预诱导 4 天，然后用氯甲基苯甲酰胺二烷基碳菁（CM-DiI）标记，然后通过经巩膜途径移植到 rd1 小鼠的视网膜下腔。在移植后 30 天收集右眼。通过全视网膜、视网膜冷冻切片和免疫荧光染色来研究移植细胞在宿主视网膜中的存活和迁移。
在视网膜下移植后，预诱导的 hPBMC 能够存活并广泛迁移到 rd1 小鼠的视网膜中。一些 CM-DiI 标记的细胞迁移到内核层和视网膜神经节细胞层。rd1 宿主小鼠视网膜下空间中的一些移植细胞表达人类光感受器特异性标记物视蛋白。
这项研究表明，预诱导的 hPBMC 可能是视网膜退行性疾病细胞替代治疗的潜在细胞来源。
