Cell Therapy of Corneal Endothelium Deficiency with Human Umbilical Mesenchymal Stem Cells
Date Issued
2010
Date
2010
Author(s)
Lee, Hsiao-Lei
Abstract
The ability of human, nonhuman primate, canine and feline corneal endothelium to proliferate is severely limited, and corneal endothelial cells hold Na+/K+ ATPase and contribute to the maintenance of the corneal transparency by their pump and barrier functions. Therefore, decompensation of endothelium would produce corneal edema. Keratoplasty is the only effective treatment for endothelial dysfunction, but there is a worldwide shortage of human donor corneas. Human umbilical mesenchymal stem cells (HUMSCs) have the potential to develop into multicells in different ex vivo culture environment, improving regenerative medicine. However, there is no evidence to prove HUMSCs could differentiate into corneal endothelium.
Hence, the objective of this study was to investigate the potential of HUMSCs transplantation to treat rabbit corneal endothelium deficiency edema. To create an animal model of corneal endothelium deficiency in New Zealand white rabbit, Mitomycin-C (MMC) anterior chamber injection and descemetohexis were used to enable the mimicking of human cornea. While descemetohexis group resulted in permanent defect of endothelium with corneal haze grade 4, the MMC group only maintained moderate cornea endothelium deficiency less than a month. HUMSCs were transplanted by the injection into anterior chamber in cell suspension (1x107 cell /μl). After transplantation, rabbits were kept in the prone position (epithelium down) for 6 hours, to improve HUMSC attachment to posterior cornea by gravity. As a result, post-transplantation did not decrease clinical corneal edema level, and histological examination revealed that dense cell clusters resided in the anterior chamber and iris. Given the fact that they possessed high N/C ratio and mitosis, it is highly suspected that the dense cell clusters were the transplanted HUMSCs. The HUMSCs survived and differentiated into various kinds of cells, and sequentially proliferated into iris epithelium and ciliary body-like tissue, in which CD31 and VEGF stain showed angiogenesis. The finding of this study also suggested that HUMSCs can survive after anterior chamber transplantation, and possess differentiation capacity. Thus, HUMSCs may have the potential to differentiate into various cells originating from the neural crest-derived mesenchymal tissue. Another discovery made by the study is the ex vivo labeled HUMSCs with CFDA-SE resulted in gradually weaker fluorescent after one week, a reason why CFDA-SE is probably not a suitable marker to trace the number and location of transplanted HUMSCs.
Subjects
corneal endothelium
corneal edema
descemetohexis
stem cell
SDGs
Type
thesis
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