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HSCI Retreat 2020 Abstract 15

3D-Printed ABCB5+ Dermal Stem Cells for the Treatment of Limbal Stem Cell Deficiency

Catherine A.A. Lee,*1,2 Jennifer A. Kunes,3 Wonhye Lee,3 Catherine S. Karpova,1 Mahtabin R. Rozbu,1 Yuzuru Sasamoto,1,2 Brian J. Wilson,2,6 Bruce R. Ksander,4 Markus H. Frank,2,5,6 Seung-schick S. Yoo,3 and Natasha Y. Frank1,2,6,7
1 Division of Genetics, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
2 Transplant Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
3 Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
4 Department of Ophthalmology, Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, MA, USA 
5 Department of Dermatology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA
6 Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
7 Department of Medicine, VA Boston Healthcare System, Boston, MA, USA
* Presenting and corresponding author: clee87@bwh.harvard.edu 

Note: Catherine A.A. Lee is currently funded by T32 EB016652-05                                                       

Submitted: Jun 11 2020; Published online: Jul 27, 2020

 

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ABSTRACT

Limbal stem cells (LSC) residing in the limbus continually repopulate the clear corneal epithelium at the front of the eye. Limbal stem cell deficiency (LSCD) occurs when these LSC are damaged (due to burns, infections, or other trauma) or missing (due to genetic conditions). Patients with LSCD are unable to regenerate the corneal epithelium, resulting in blindness due to conjunctival in-growth and neovascularization. Unilateral LSCD can be treated by transplantation of autologous limbal tissue or ex vivo expanded limbal cells from the unaffected eye, however, patients with bilateral LSCD have no source of autologous LSC. Treatment with allogeneic limbal tissue from cadaveric donors has a less favorable outcome and typically provides only temporary relief without long-term restoration of the corneal epithelium. Our lab discovered that ABCB5 is a specific marker of LSC and that ABCB5+ LSC can restore the corneal epithelium in a LSCD mouse model. We also discovered that ABCB5 marks dermal stem cells (DSC) and performed a preliminary pilot study demonstrating the ability of ABCB5+ DSC to express the corneal epithelial markers PAX6 and KRT12 in culture. Furthermore, transplantation of human ABCB5+ DSC in a LSCD mouse model led to the formation of clear corneas. We are currently using 3D bioprinting technology to develop a stem cell-based corneal-limbal bio-prosthesis that can be implanted into wounded corneas. The use of ABCB5+ DSCs as an alternative autologous source of LSC and 3D-printing to recreate the LSC niche has the potential to greatly improve therapy for patients with bilateral LSCD.