Young bone marrow Sca-1 cells protect aged retina from ischaemia-reperfusion injury through activation of FGF2.

Young bone marrow Sca-1 cells protect aged retina from ischaemia-reperfusion injury through activation of FGF2.
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年轻的骨髓 Sca-1 细胞通过激活 FGF2 来保护老化的视网膜免受缺血再灌注损伤。

DOI:
10.1111/jcmm.13905
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发表时间:
2018-12
影响因子:
5.3
通讯作者:
Li RK
Li RK
中科院分区:
医学2区
文献类型:
--
作者:
Shao Z;Wu J;Du G;Song H;Li SH;He S;Li J;Wu J;Weisel RD;Yuan H;Li RK

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视网膜神经节细胞凋亡和视神经变性在老年患者中普遍存在,这可能与骨髓(BM)干细胞数量/功能下降有关,因为这两种器官之间可能存在串扰。视网膜缺血再灌注(I/R)损伤加速了这一病理过程。本研究探讨了年轻的骨髓干细胞是否可以在急性I/R损伤后再生和修复老化的视网膜。将年轻的BM干细胞抗原1阳性(Sca-1+)或Sca-1−细胞移植到致死辐射的老年受体小鼠中,分别产生Sca-1+和Sca-1−嵌合体。将动物圈养3个月,以使年轻的Sca-1细胞在老年小鼠的BM中重新繁殖。然后通过眼内压升高诱导视网膜I/R。伤后7天,Sca-1+比Sca-1-chimaeras更好地保留了视觉功能。更多的Sca-1+细胞比Sca-1-细胞归巢到视网膜,并且在Sca-1+嵌合体中更多的细胞分化成神经胶质细胞和小神经胶质细胞。损伤后,视网膜中的Sca-1+细胞减少宿主细胞凋亡,这与Sca-1+嵌合体中成纤维细胞生长因子2(FGF 2)的高表达相关。年轻的Sca-1+细胞通过FGF 2和Akt信号通路重新填充老年视网膜中的干细胞,并减少急性I/R损伤后的细胞凋亡。
Retinal ganglion cell apoptosis and optic nerve degeneration are prevalent in aged patients, which may be related to the decrease in bone marrow (BM) stem cell number/function because of the possible cross‐talk between the two organs. This pathological process is accelerated by retinal ischaemia‐reperfusion (I/R) injury. This study investigated whether young BM stem cells can regenerate and repair the aged retina after acute I/R injury. Young BM stem cell antigen 1 positive (Sca‐1+) or Sca‐1− cells were transplanted into lethally irradiated aged recipient mice to generate Sca‐1+ and Sca‐1− chimaeras, respectively. The animals were housed for 3 months to allow the young Sca‐1 cells to repopulate in the BM of aged mice. Retinal I/R was then induced by elevation of intraocular pressure. Better preservation of visual function was found in Sca‐1+ than Sca‐1− chimaeras 7 days after injury. More Sca‐1+ cells homed to the retina than Sca‐1− cells and more cells differentiated into glial and microglial cells in the Sca‐1+ chimaeras. After injury, Sca‐1+ cells in the retina reduced host cellular apoptosis, which was associated with higher expression of fibroblast growth factor 2 (FGF2) in the Sca‐1+ chimaeras. Young Sca‐1+ cells repopulated the stem cells in the aged retina and diminished cellular apoptosis after acute I/R injury through FGF2 and Akt signalling pathways.
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