Injectable biomaterial-mediated transplantation for treatment of limbal stem cell deficiency скачать в хорошем качестве

Injectable biomaterial-mediated transplantation for treatment of limbal stem cell deficiency

The corneal epithelium is maintained by limbal stem cells (LSCs) which reside in the limbus, an intermediate zone of conjunctiva and cornea. Loss of LSCs result in limbal stem cell deficiency (LSCD). Patients with LSCD suffer from vision loss due to cloudy conjunctiva invading the clear cornea. Unilateral LSCD can be treated with the transplantation of autologous limbal tissue. However, patients with bilateral LSCD have to rely on allogeneic transplantation, which has a relatively poor clinical outcome. Moreover, the shortage of corneal donors limits the availability of allogeneic transplants. There is, therefore, a critical need to develop a novel therapy to treat LSCD that also addresses the donor shortage. Previous studies showed the involvement of limbal fibroblasts in the maintenance of LSCs. Therefore, the goal of the study is to demonstrate the effectiveness of transplanting limbal fibroblasts via direct injection within a cell-protective shear-thinning protein-based biomaterial under the conjunctiva to treat LSCD. Proposed study will evaluate the function of gel-encapsulated limbal fibroblasts (Aim 1) and establish gel-encapsulated limbal fibroblast injection for the treatment of mouse LSCD (Aim 2). In addition to the limbal fibroblasts expanded from human donor corneas, we will also transplant induced pluripotent stem cell (iPSC)-derived limbal fibroblasts. Successful completion of this application will provide us with another strategic option to treat LSCD, allowing us to conduct larger animal experiments and ultimately, apply this treatment to LSCD patients. The infinite production of limbal fibroblasts from iPSCs has the potential to overcome the donor shortage.