Stem Cell Spheres for Corneal Regeneration
Corneal cells isolated from the peripheral cornea and limbus can be cultured in vitro under sphere-forming conditions which enrich for stem and progenitor cells. These stem cell-enriched spheres represent a mixed population of cells comprising epithelial, limbal and stromal components which show promise as transplantable elements for corneal regeneration. Spheres are responsive to collagen stimulus and display dynamic behaviours that include directed cell migration, en masse sphere migration and cell proliferation and differentiation. Characterization of cells within spheres confirms retention of stem cell markers, while migratory cells express both stromal and epithelial cell differentiation markers. Upon mechanical injury, spheres respond with similar patterns akin to the wound healing response seen in vivo. Implantation of spheres into decellularized normal and diseased corneal tissue invokes a proliferative and migratory response preferentially over the corneal surface with some evidence of limbal reformation. Collectively, these findings suggest stem cell-enriched spheres may be used in future cell-based therapy as a way to introduce a well-defined and characterized stem cell population for the treatment of limbal stem cell deficiency and corneal dystrophies.
KeywordsCornea Stem cell Spheres Cell differentiation Cell migration Cell proliferation Limbus Sphere-forming assay Cell therapy Corneal regeneration
Compliance with Ethical Requirements
Conflict of Interest
Salim Ismail, Charles N. J. McGhee, Jennifer J. McGhee, Ye Li, Jeremy John Mathan, Jinny Jung Yoon, Himanshu Wadhwa, Stephanie U-Shane Huang and Trevor Sherwin declare that they have no conflict of interest.
Informed Consent/Human Studies
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
No animal studies were carried out by the authors for this article.
- 19.Galindo S, Herreras JM, Lopez-Paniagua M, Rey E, de la Mata A, Plata-Cordero M, et al. Therapeutic effect of human adipose tissue-derived mesenchymal stem cells in experimental corneal failure due to limbal stem cell niche damage. Stem Cells (Dayton, Ohio). 2017;35(10):2160–74.PubMedCrossRefGoogle Scholar
- 46.Kolli S, Ahmad S, Lako M, Figueiredo F. Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells (Dayton, Ohio). 2010;28(3):597–610.Google Scholar