The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury.
To investigate the anti-inflammatory and anti-angiogenic effects of mesenchymal stem cells (MSC) in the chemically burned corneas, we mechanically removed the corneal epithelium of rats after 100% alcohol instillation. The rats were then randomized into four groups: fresh media, conditioned media derived from the MSC culture (MSC-CM), MSC applied topically to the damaged corneas for 2 hours immediately after the injury or MSC-CM applied either once or 3 times per day for 3 consecutive days. Corneal surface was evaluated every week. After 3 weeks, the corneas were stained with the hematoxylin-eosin, and the expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-6, IL-10, transforming growth factor (TGF)-beta1, thrombospondin-1 (TSP-1), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) were analyzed. CD4+ cells were assessed in the corneas. We found that both MSC and three-time applied MSC-CM (1) reduced corneal inflammation and neovascularization, (2) decreased IL-2 and IFN-gamma, although increased IL-10 and TGF-beta1 as well as IL-6, (3) reduced the infiltration of CD4+ cells, and (4) upregulated the expression of TSP-1, although downregulated that of MMP-2. Interestingly, whereas three-time application of MSC-CM was partially effective, transplantation of MSC achieved a better outcome in suppressing corneal inflammation. The results of this study suggest that the anti-inflammatory and anti-angiogenic action of MSC in the chemically burned corneas might be mediated in part through paracrine pathways involving soluble factors such as IL-10, TGF-beta1, IL-6 and TSP-1.
Oh
Joo Youn
JY
Department of Ophthalmology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Korea.
Kim
Mee Kum
MK
Shin
Mi Sun
MS
Lee
Hyun Ju
HJ
Ko
Jung Hwa
JH
Wee
Won Ryang
WR
Lee
Jin Hak
JH
D000818:Animals; D002057:Burns, Chemical / Q000473:pathology / Q000601:surgery*; D002460:Cell Line; D002478:Cells, Cultured; D003315:Cornea / Q000473:pathology / Q000601:surgery; D065306:Corneal Injuries; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000502:physiology*