Corneal Stromal Stem Cell: Methods for Ex Vivo Expansion

  • Olena Al-Shymali
  • Jorge L. Alió del Barrio
  • James L. FunderburghEmail author
Part of the Essentials in Ophthalmology book series (ESSENTIALS)


The cornea is a transparent, well-organized connective tissue that provides two-thirds of the eye’s total refractive power. The centermost layer of the cornea is the stroma that makes up approximately 90% of the corneal volume. The corneal stromal limbus contains anatomical features, named the palisades of Vogt, that form a niche for both limbal epithelial stem cells (LESCs) and corneal stromal stem cells (CSSC). CSSC are derived from the neural crest as they express genes typical for descendants of the neural ectoderm such as PAX6, Six2, Six3, and Notch1. The adult stem cell marker ABCG2 is well expressed by CSSC. Moreover, CSSC express mesenchymal stem cell (MSC) markers such as CD73, CD90, and CD166. They exhibit clonal growth, self-renewal properties, and a potential for differentiation into multiple distinct tissue types. Upon the incubation in a keratocyte differentiation medium, CSSC showed the potential to differentiate into a keratocyte by producing extracellular matrix components that in adults are uniquely expressed in the corneal stroma such as keratocan, keratan sulfate, and aldehyde dehydrogenase 3A1. Several studies and the anatomical proximity of LESC and CSSC populations in the limbal niche suggest that the principal role of CSSC in vivo is the homeostatic maintenance of the LESC. Human CSSC do not trigger a xenogeneic T-cell-mediated immune response reaction in vivo and suppress T-cell proliferation in vitro. These findings support an immunomodulatory function for CSSC and the potential use of allogeneic CSSC in different cell-based or tissue-engineered therapeutic applications.


Corneal stromal stem cells Stroma Limbal epithelial stem cells Limbal stem cells Limbal niche Niche cells Mesenchymal stem cells Keratocyte 


Conflict of Interest

Olena Al-Shymali: no conflict of interest

Jorge L. Alio del Barrio: no conflict of interest

James L. Funderburgh: no conflict of interest

Informed Consent

No human studies were carried out by the authors for this article.

Animal Studies

No animal studies were carried out by the authors for this article.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Olena Al-Shymali
    • 1
  • Jorge L. Alió del Barrio
    • 2
  • James L. Funderburgh
    • 3
    Email author
  1. 1.Vissum CorporationAlicanteSpain
  2. 2.University Miguel HernandezVissum-Instituto Oftalmologico de AlicanteAlicanteSpain
  3. 3.University of Pittsburgh, Department of OphthalmologyPittsburghUSA

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