Limbal Stem Cells
Descemet's Membrane Transplant Technology
Limbal stem cell deficiency (LSCD) is a blinding condition caused by the loss of LSCs, a population of unipotent/oligopotent cells located in the limbus, the transition zone between the cornea and conjunctiva (Fig 1). LSCs continuously regenerate the vital, transparent corneal epithelium throughout life. Loss of these cells from ocular surface trauma and other conditions leads to corneal scarring, chronic pain, and blindness. Globally, LSCD accounts for an estimated 15–20% of corneal blindness. Furthermore, clinical data from the University of Minnesota Eye Clinic (provided by Dr. Joshua Hou) indicate that 4.25% of corneal patients present with LSCD, with 56% requiring surgical intervention. While treatments with variable efficacy exist for partial LSCD where residual limbal stem cells remain, severe cases lacking any viable LSCs (total LSCD) require the transplantation of healthy donor LSCs for visual rehabilitation. However, due to the high risk of rejection associated with these procedures, long-term outcomes remain limited.
To address these limitations, Medical Director Dr. Joshua Hou, Dr. Ching Yuan, and Peter Bedard from the LGS R&D team developed a novel Descemet’s membrane (DM)-based therapy (detailed in the U.S. patent below) that restores the transparent, protective tissue layer of the cornea in both partial and total LSCD. The key to this approach is establishing a healthy, stable microenvironment for corneal epithelial stem cells to thrive on the ocular surface, thereby unlocking the native regenerative potential of limbal stem cells to restore visual clarity and ocular function in patients suffering from surface burns, trauma, and debilitating corneal diseases. Compared to the current standard of care (amniotic membrane), DM grafts are more resistant to degradation on the ocular surface, better maintain LSC stemness, and offer full optical transparency without postoperative visual blurring (Reference 1).
Figure 1. Restoration of a healthy ocular surface by transplanting limbal stem cell construct to patient's affected eye.
Figure 2. DM-limbal ring airlift organ culture model. DM-limbal rings were prepared from a Corneoscleral disc and then cultured to allow limbal stem cells to expand from the limbal niche on to the anterior side of DM. Step 1- Decellularized DM was separated from posterior storm by pneumodissection to form a type 2 big bubble air pocket. Step 2- The air pocket was propagated to the limbus to fully separate DM from anterior cornea. Step 3- Anterior layers of stroma were excised, leaving behind a DM-limbal ring construct with DM attached 360 degrees to the limbus. Step 4(a)- DM-limbal ring was cultured under submersion conditions until confluence. Step 4(b)- Once confluent, some DM-limbal ring constructs were airlifted by lowering culture media levels, exposing the limbal cell down growth layer to air to induce stratification. Image credit 2023 Lauren Kalinoski, MS, CMI
In partnership with industry sponsor BrightStar Therapeutics LLC, LGS has successfully incubated this novel stem cell technology and developed two products: BrightMEM™ for partial LSCD and BrightSTEM™ for total LSCD (Fig 2). In 2023, LGS and BrightStar Therapeutics started providing BrightMEM to corneal surgeons to perform a new procedure termed Descemet Membrane Anterior Keratoplasty (DMAK, Fig 3). To date, more than 700 DMAK procedures have been performed across the United States and Japan for patients with partial LSCD. A 2026 retrospective review demonstrated that this DM-based technology significantly improves outcomes in partial LSCD, achieving up to a 97.1% complete healing rate and visual acuity improvement in 52.6% of patients (Reference 2). DMAK has since gained widespread adoption among corneal surgeons, rapidly becoming the fourth most common corneal transplant procedure in the U.S.
Building on the clinical success of BrightMEM™, BrightStar Therapeutics continues its collaboration with LGS to advance BrightSTEM™ through Investigational New Drug (IND)-enabling preclinical and regulatory studies to treat total LSCD. These ongoing translational efforts focus on establishing the safety, potency, and manufacturing protocols required for an IND submission. Securing regulatory clearance will pave the way for upcoming clinical trials, bringing a definitive cell-replacement therapy to patients suffering from otherwise untreatable corneal blindness.
Ref No. 1: Descemet Membrane Versus Amniotic Membrane for Limbal Stem Cell Therapy. Cornea. 2026, 45(5):631-639.
Ref No. 2: Descemet Membrane Anterior Keratoplasty With BrightMEM Corneal Allograft: An Innovative Technique for Treatment of Nonhealing Diseases of the Ocular Surface. Cornea. 2026, 45(8):1068-1072
U.S. Patent No. 12,383,655 B2; EU Utility Patent No. 3867357