Action at a Distance: Systemically Administered Adult Stem/Progenitor Cells (MSCs) Reduce Inflammatory Damage to the Cornea Without Engraftment and Primarily by Secretion of TNF-α Stimulated Gene/Protein 6
Action at a Distance: Systemically Administered Adult Stem/Progenitor Cells (MSCs) Reduce Inflammatory Damage to the Cornea Without Engraftment and Primarily by Secretion of TNF-α Stimulated Gene/Protein 6
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DOI：
10.1002/stem.708
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发表时间：
2011-10-01
期刊：
影响因子：
5.2
通讯作者：
Prockop, Darwin J.
中科院分区：
文献类型：
--
作者：
Roddy, Gavin W.;Oh, Joo Youn;Prockop, Darwin J.
先前的报道表明，化学损伤对角膜的有害影响通过局部或全身施用来自骨髓的成体干/祖细胞（称为间充质干细胞或基质细胞（MSC））而得到改善。然而，MSC对损伤角膜的有益作用的机制尚不清楚。在此，我们证明了人MSC（hMSC）在腹膜内（i. p.）或静脉注射（i. v.）在对大鼠角膜进行化学损伤后给药。对甘油醛3-磷酸脱氢酶（GAPDH）的人mRNA的定量测定表明，在静脉内或腹膜内给予1 × 10（7）hMSC后1天和3天，大鼠角膜中存在少于10个hMSC。使用transwell共培养系统的体外实验表明，角膜上皮细胞的化学损伤激活hMSCs分泌多能抗炎蛋白TNF-α刺激的基因/蛋白6（TSG-6）。在体内，静脉注射hMSC的效果在很大程度上被TSG-6的敲低所消除。此外，通过静脉内或局部施用TSG-6基本上复制了hMSC的作用。因此，结果表明，全身施用的hMSC减少了对角膜的炎性损伤，而无需植入，并且主要通过响应于来自角膜的损伤信号而分泌抗炎蛋白TSG-6。干细胞2011;29：1572-1579
Previous reports demonstrated that the deleterious effects of chemical injury to the cornea were ameliorated by local or systemic administration of adult stem/progenitor cells from bone marrow referred to as mesenchymal stem or stromal cells (MSCs). However, the mechanisms for the beneficial effects of MSCs on the injured cornea were not clarified. Herein, we demonstrated that human MSCs (hMSCs) were effective in reducing corneal opacity and inflammation without engraftment after either intraperitoneal (i.p.) or intravenous (i.v.) administration following chemical injury to the rat cornea. A quantitative assay for human mRNA for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) demonstrated that less than 10 hMSCs were present in the corneas of rats 1-day and 3 days after i.v. or i.p. administration of 1 x 10(7) hMSCs. In vitro experiments using a transwell coculture system demonstrated that chemical injury to corneal epithelial cells activated hMSCs to secrete the multipotent anti-inflammatory protein TNF-alpha stimulated gene/protein 6 (TSG-6). In vivo, the effects of i.v. injection of hMSCs were largely abrogated by knockdown of TSG-6. Also, the effects of hMSCs were essentially duplicated by either i.v. or topical administration of TSG-6. Therefore, the results demonstrated that systemically administered hMSCs reduce inflammatory damage to the cornea without engraftment and primarily by secretion of the anti-inflammatory protein TSG-6 in response to injury signals from the cornea. STEM CELLS 2011;29:1572-1579