Home Blog of Signal Transduction Stem Cells & Wnt TGF-beta/Smad Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency

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Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency

Approximately 10 million individuals have blindness due to limbal stem cell (LSCs) deficiency, one of the most challenging problems in ophthalmology. To replenish the LSC pool, an autologous extraocular cell source is appropriate, thereby avoiding the risk of immune rejection, the need for immunosuppression and the risk of damaging the contralateral eye. In recent years, adipose-derived mesenchymal stem cells (ADSCs) have been a key element in ocular regenerative medicine. In this study, we developed a protocol for deriving human LSCs from ADSCs compatible with the standard carrier human amniotic membrane, helping provide a stem cell pool capable of maintaining proper corneal epithelial homeostasis. The best protocol included an ectodermal induction step by culturing ADSCs with media containing fetal bovine serum, transforming growth factor-β inhibitor SB-505124, Wnt inhibitor IWP-2 and FGF2 for 7 days, followed by an LSC induction step of culture in modified supplemental hormonal epithelial medium supplemented with pigment epithelium-derived factor and keratinocyte growth factor for 10 additional days. The optimal differentiation efficiency was achieved when cells were cultured in this manner over vitronectin coating, resulting in up to 50% double-positive αp63/BMI-1 cells. The results of this project will benefit patients with LSC deficiency, aiding the restoration of vision.

 

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This study presents a protocol for deriving human limbal stem cells (LSCs) from adipose-derived mesenchymal stem cells (ADSCs) using a standard carrier, human amniotic membrane, to help maintain proper corneal epithelial homeostasis. LSC deficiency is a challenging problem in ophthalmology, affecting around 10 million individuals worldwide, and the use of autologous extraocular cell sources such as ADSCs may help avoid immune rejection and the need for immunosuppression.

The protocol involved an ectodermal induction step using media containing fetal bovine serum, transforming growth factor-β inhibitor SB-505124, Wnt inhibitor IWP-2, and FGF2 for seven days, followed by an LSC induction step using modified supplemental hormonal epithelial medium supplemented with pigment epithelium-derived factor and keratinocyte growth factor for ten additional days. The study found that the optimal differentiation efficiency was achieved when cells were cultured over vitronectin coating, resulting in up to 50% double-positive αp63/BMI-1 cells.

Overall, this study provides valuable insights into the use of ADSCs for ocular regenerative medicine and offers a potential solution for restoring vision in patients with LSC deficiency.

Related Products

Cat.No. Product Name Information
S2186 SB505124 SB505124 is a selective inhibitor of TGFβR for ALK4, ALK5 with IC50 of 129 nM and 47 nM in cell-free assays, respectively, also inhibits ALK7, but does not inhibit ALK1, 2, 3, or 6.

Related Targets

TGF-beta/Smad