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First published online December 6, 2007
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2007-0653v1
26/2/570    most recent
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Submitted on August 7, 2007
Accepted on November 27, 2007

TRANSLATIONAL AND CLINICAL RESEARCH

Adipose-Derived Stem Cells are a Source for Cell Therapy of The Corneal Stroma

F. Arnalich-Montiel 1, S. Pastor 2, A. Blazquez-Martinez 1, J. Fernandez-Delgado 3, M. Nistal 4, J. L. Alio 2, M. P. De Miguel 1*

1 Cell Engineering Laboratory, La Paz University Hospital, Madrid, Spain
2 Vissum Ophtalmological Institute of Alicante, and Miguel Hernandez University, Alicante, Spain
3 Plastic and Reconstructive Surgery Department, La Paz University Hospital, Madrid, Spain
4 Pathology Department, La Paz University Hospital, Madrid, Spain

* To whom correspondence should be addressed. E-mail: maria.demiguel{at}uam.es.


   Abstract

Most corneal diseases affect corneal stroma, and include immune or infectious diseases, ecstatic disorders, traumatic scars and corneal dystrophies. Cell-based therapy is a promising therapeutic approach to overcome the current disadvantages of corneal transplantation. We aimed to search for a cell source to repopulate and regenerate corneal stroma.

We investigated the ability of human processed lipoaspirate-derived (PLA) cells to regenerate corneal stroma in experimental animals. In a first set of experiments, we tested the biosafety and immunogenicity of human PLA stem cells transplanted into the corneal stroma of rabbits. No immune response was elicited even though we used immunecompetent animals. PLA cells survived up to 10 weeks post-transplant, maintained their shape and remained intermingled between the stroma without disrupting its histological pattern. Interestingly, transparency was preserved even 10 weeks after the transplant, when PLA cells formed a discontinuous layer in the stroma. In a second set of experiments, regeneration of the corneal stroma by PLA cells was assessed, creating a niche by partial ablation of the stroma. After 12 weeks, human cells were disposed following a multilayered pattern, and differentiated into functional keratocytes, as assessed by the expression of aldehyde-3-dehydrogenase and cornea-specific proteoglycan keratocan.

Based on our results, we believe that adipose-derived adult stem cells can be a cell source for stromal regeneration and repopulation in diseased corneas. The low health impact of the surgical procedure performed to obtain the PLA cells provides this cell source with an additional beneficial feature for their possible future autologous use in human patients.

Key Words. Cornea, cell therapy, adipose-derived stem cells, Mesenchymal stem cells, transplant, keratocan, stem cells transplantation, keratocyte







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