Naylor Richard W, McGhee Charles N J, Cowan Chad A, Davidson Alan J, Holm Teresa M, Sherwin Trevor
Department of Ophthalmology, University of Auckland, Auckland 1142, New Zealand.
Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, United States of America.
PLoS One. 2016 Oct 28;11(10):e0165464. doi: 10.1371/journal.pone.0165464. eCollection 2016.
Corneal diseases such as keratoconus represent a relatively common disorder in the human population. However, treatment is restricted to corneal transplantation, which only occurs in the most advanced cases. Cell based therapies may offer an alternative approach given that the eye is amenable to such treatments and corneal diseases like keratoconus have been associated specifically with the death of corneal keratocytes. The ability to generate corneal keratocytes in vitro may enable a cell-based therapy to treat patients with keratoconus. Human induced pluripotent stem cells (hiPSCs) offer an abundant supply of cells from which any cell in the body can be derived. In the present study, hiPSCs were successfully differentiated into neural crest cells (NCCs), the embryonic precursor to keratocytes, and then cultured on cadaveric corneal tissue to promote keratocyte differentiation. The hiPSC-derived NCCs were found to migrate into the corneal stroma where they acquired a keratocyte-like morphology and an expression profile similar to corneal keratocytes in vivo. These results indicate that hiPSCs can be used to generate corneal keratocytes in vitro and lay the foundation for using these cells in cornea cell-based therapies.
诸如圆锥角膜之类的角膜疾病在人群中是一种相对常见的病症。然而，治疗方法仅限于角膜移植，而这仅在最严重的病例中才会进行。鉴于眼睛适合此类治疗，且像圆锥角膜这样的角膜疾病与角膜基质细胞的死亡有特定关联，基于细胞的疗法可能提供一种替代方法。体外生成角膜基质细胞的能力或许能使基于细胞的疗法用于治疗圆锥角膜患者。人诱导多能干细胞（hiPSC）可提供丰富的细胞来源，能从中分化出体内任何类型的细胞。在本研究中，hiPSC成功分化为神经嵴细胞（NCC），即角膜基质细胞的胚胎前体细胞，然后在尸体角膜组织上培养以促进角膜基质细胞分化。研究发现，hiPSC来源的NCC迁移到角膜基质中，在那里它们获得了类似角膜基质细胞的形态以及与体内角膜基质细胞相似的表达谱。这些结果表明，hiPSC可用于体外生成角膜基质细胞，并为在基于角膜细胞的疗法中使用这些细胞奠定了基础。
