Bioengineering and stem cells for corneal endothelial cell therapy

The global planetary scarcity for corneal donation pushes research teams to develop substitution strategies. The worldwide success of endothelial keratoplasty (EK) has profoundly simplified the paradigm of corneal bioengineering since the technical and biological requirements for EK is far simpler than for full thickness corneas. Two main concepts have recently emerged: bioengineered endothelial cell (EC) sheets inserted into the anterior chamber or EC suspension ready to be injected. Review of the literature and personal works from our laboratory of corneal bioengineering. According to the local availability of donors, researchers either focus on the optimization of the use of human corneas or on the development of alternative substitutes comprising transformation of primarily non-ocular human cell types (hECS, hIPS or MSC) and bioartificial or animal decellularized substrates as a carrier. We chose to use only human tissues and developped different methods able to multiply the EK available. With femtosecond laser cut, 5 to 7 EK seemed feasible with 1 donor. We also patented a corneal bioreactor helpful during the bioengineering process itself as well as for preclinical validation of the new advanced therapeutic medicinal products on ex vivo human corneas. Numerous proofs of concepts have been obtained and several preclinical animals studies done. The very first-in-man applications was done in Japan with injection of cultured EC. All these promising complementary strategies may constitute the tomorrow endothelial dysfunction treatments. Grants: ABM 2013, ANSM 2012, EFS 2012