Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.
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DOI：
10.1371/journal.pone.0062703
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ding X
中科院分区：
文献类型：
--
作者：
Yu X;Lu C;Liu H;Rao S;Cai J;Liu S;Kriegel AJ;Greene AS;Liang M;Ding X
间充质干细胞（MSC）的管理是已知的，以提高肾脏损伤后的恢复。在这里，我们测试了低氧预处理的MSC移植通过改善MSC向受损肾脏的迁移来增强细胞疗法对急性肾损伤（阿基）的功效的潜力。钴作为低氧模拟预处理（HMP）。MSC在200 µmol/L钴中培养24 h后接受HMP。与常氧培养的MSC（NP-MSC）相比，HMP可显著增加MSC中HIF-1α和CXCR 4的表达，并促进MSC的体外迁移。当用靶向HIF-1α或CXCR 4拮抗剂的siRNA处理MSC时，这种作用丧失。将SPIO标记的MSC给予I/R损伤的大鼠，随后立即进行磁共振成像。成像清楚地显示，HMP-MSC表现出更大的迁移和更长的保留时间在缺血的肾脏比NP-MSC。组织学评价显示缺血肾的肾小球毛细血管中HMP-MSC比接受NP-MSC的肾中更多。HMP组肾小管偶见铁标记，NP组肾小管未见铁标记，提示HMP后肾小管转分化的可能性。这些结果也通过使用CM-DiI标记的荧光显微镜研究得到了证实。HMP-MSC募集增加与肾损伤减少和功能恢复增强相关。这种作用也与HMP-MSC增加的旁分泌作用有关。因此，我们认为，通过增强MSC迁移和延长肾脏滞留，MSC低氧预处理可能是一个有用的方法，为发展阿基细胞治疗。
Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP). MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC), HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.
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影响因子：
4.4
作者：
Ittrich, Harald;Lange, Claudia;Nolte-Ernsting, Claus
通讯作者：
Nolte-Ernsting, Claus
影响因子：
4.2
作者：
Ishikawa, Tohru;Nakashiro, Koh-ichi;Hamakawa, Hiroyuki
通讯作者：
Hamakawa, Hiroyuki
影响因子：
56.9
作者：
GOLDBERG, MA;DUNNING, SP;BUNN, HF
通讯作者：
BUNN, HF
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
5.2
作者：
Honczarenko, Marek;Le, Yi;Silberstein, Leslie E.
通讯作者：
Silberstein, Leslie E.