Has biomaterial-free oral mucosal epithelial cell sheet transplantation been used in humans for the treatment of limbal stem cell deficiency before 2013?

Biomaterial-Free Oral Mucosal Epithelial Cell Sheet Transplantation for Limbal Stem Cell Deficiency Before 2013

Based on the available evidence, biomaterial-free oral mucosal epithelial cell sheet transplantation was not used in humans for treating limbal stem cell deficiency before 2013. The earliest documented clinical trial of biomaterial-free cultured oral mucosal epithelial cell sheets (COMECs) was registered as NCT02149732 and published in 2018 1.

Historical Development of Oral Mucosal Epithelial Transplantation

Pre-2013 Approaches

• Prior to 2013, treatment of limbal stem cell deficiency (LSCD) primarily involved:
  • Conventional methods such as conjunctival-limbal autograft (CLAU), conjunctival-limbal allograft (CLAL), and kerato-limbal allograft (KLAL) surgeries 2
  • Cultivated limbal epithelial transplantation (CLET) using carrier materials 2
  • Cultivated oral mucosal epithelial transplantation (COMET) using carriers such as amniotic membrane 2, 3

Carrier-Based COMET Before 2013

• The earliest documented COMET procedures used human amniotic membrane as a carrier:
  • Long-term outcomes of COMET using amniotic membrane carriers were reported in a 2011 study with a mean follow-up of 25.5 months 4
  • This carrier-based approach showed promising results with corneal surface stability of 64.8% at 1 year and 53.1% at 3 years 4

Biomaterial-Free Approach Development

First Documented Biomaterial-Free Approach

• The first documented clinical trial of biomaterial-free COMECs was published in 2018 1
• This prospective clinical trial (NCT02149732) specifically noted:
  • COMECs were "prepared in a culture system without the use of any temperature-sensitive polymers or carriers"
  • The cell sheets were transplanted without suture fixation
  • The trial demonstrated successful ocular surface reconstruction in 75% of cases

Technical Evolution

• By 2016, standardized protocols had been established that could promote growth and differentiation of cells from oral mucosal biopsies into corneal lineage using recombinant epidermal growth factor and insulin 5
• However, these protocols were still primarily using carrier materials rather than biomaterial-free approaches

Clinical Implications of Biomaterial-Free Approach

Advantages Over Carrier-Based Methods

• Biomaterial-free approaches potentially offer:
  • Reduced risk of immunological reactions to carrier materials
  • More direct integration with host tissue
  • Simplified surgical technique without need for suture fixation 1

Patient Selection Considerations

• The 2018 study found that biomaterial-free COMEC transplantation failed in eyes with full symblepharon in all four quadrants 1
• This suggests careful patient selection is critical for success with this technique

Conclusion

The evidence clearly indicates that while carrier-based oral mucosal epithelial transplantation was being performed before 2013, the specific biomaterial-free technique was not documented in human clinical use until the 2018 publication of the NCT02149732 trial. This represents an important technical advancement in the treatment of limbal stem cell deficiency that emerged after 2013.