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Corneal Stromal Stem Cell Transplantation Induces Recovery from Corneal Scarring

Review of “Corneal stromal stem cells restore corneal transparency after N2-injury in mice” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While corneal allografts represent the gold-standard treatment for non-inflammatory diseases that lead to vision loss, the severe lack of donor tissues has prompted the search for new approaches that include the application of a rare population of multipotent corneal stromal stem cells resident in the human cornea (Read the original STEM CELLS study here!) [1]. This easy to obtain stem cell-type [2] has been employed in ocular regeneration (See the original STEM CELLS study here!) [3] and in the generation of corneal tissues that mimic the human cornea [4-7]. 

In a recent STEM CELLS Translational Medicine article [8], researchers led by Vincent M. Borderie (Sorbonne Université, Paris, France) describe the results of a study that evaluated the potential of corneal stromal stem cells to promote the regeneration of transparent stromal tissue after corneal scarring induced by liquid nitrogen. Excitingly, Ghoubay et al. now report that corneal stromal stem cell therapy can reverse liquid nitrogen-associated alterations in the cornea in a mouse model, restore corneal transparency, and ameliorate vision loss.

The authors first developed a mouse model of corneal stromal scar, which they induced through the application of liquid nitrogen after epithelial debridement. This mode of injury prompted an early inflammatory response that was followed by common cellular events that occur after corneal injury, such as the apoptosis of keratocytes and the transformation of keratocytes into myofibroblasts. A later inflammatory response induced known features of the corneal scarring process, such as the synthesis of collagen type III, the impairment of stromal ultrastructure, the induction of corneal stromal haze, and an increase in corneal rigidity. 

Encouragingly, the injection of corneal stromal stem cells into the injured cornea at the late phase of inflammation led to a general reversal of liquid nitrogen-induced injuries, with corneal stromal stem cell migration and growth in the recipient stroma accompanied by an improvement in corneal transparency and the recovery of lost vision. Furthermore, corneal stromal stem cell therapy also dampened the inflammatory response, induced recipient corneal epithelial cell growth, decreased collagen type III stromal content, restored the stromal ultrastructure, and decreased corneal rigidity.

Corneal stromal stem cells can be easily retrieved and cultured from patient or donor eyes and, overall, this study provides robust preclinical evidence for the utility of these cells in the treatment of corneal scarring through the regeneration of transparent stromal tissue.

For more on the therapeutic potential of corneal stromal stem cells in the treatment of vision loss, stay tuned to the Stem Cells Portal!

References

  1. Du Y, Funderburgh ML, Mann MM, et al., Multipotent Stem Cells in Human Corneal Stroma. STEM CELLS 2005;23:1266-1275.
  2. Basu S, Hertsenberg AJ, Funderburgh ML, et al., Human limbal biopsy–derived stromal stem cells prevent corneal scarring. Science Translational Medicine 2014;6:266ra172.
  3. Du Y, Carlson EC, Funderburgh ML, et al., Stem Cell Therapy Restores Transparency to Defective Murine Corneas. STEM CELLS 2009;27:1635-1642.
  4. Du Y, SundarRaj N, Funderburgh ML, et al., Secretion and Organization of a Cornea-like Tissue In Vitro by Stem Cells from Human Corneal Stroma. Investigative Ophthalmology & Visual Science 2007;48:5038-5045.
  5. Wu J, Du Y, Mann MM, et al., Corneal stromal stem cells versus corneal fibroblasts in generating structurally appropriate corneal stromal tissue. Experimental Eye Research 2014;120:71-81.
  6. Wu J, Du Y, Mann MM, et al., Bioengineering Organized, Multilamellar Human Corneal Stromal Tissue by Growth Factor Supplementation on Highly Aligned Synthetic Substrates. Tissue Engineering Part A 2013;19:2063-2075.
  7. Wu J, Du Y, Watkins SC, et al., The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. Biomaterials 2012;33:1343-1352.
  8. Ghoubay D, Borderie M, Grieve K, et al., Corneal stromal stem cells restore transparency after N2 injury in mice. STEM CELLS Translational Medicine 2020;9:917-935.