Research and Development Department, Tissue Tech, Inc., and Ocular Surface Center Miami, FL, USA.
Curr Mol Med. 2010 Dec;10(9):841-50. doi: 10.2174/156652410793937796.
The stem cells (SCs) of the corneal epithelium located in the limbal basal layer are the ultimate source to maintain corneal epithelial homeostasis. Like other adult tissue-specific SCs, self renewal and fate decision of limbal SCs are regulated by a specialized in vivo microenvironment, termed "niche". Loss of limbal SCs or dysfunction of the limbal niche renders corneas with a unique clinical disease labeled limbal stem cell deficiency (LSCD). Besides transplantation of autologous or allogeneic limbal SCs or amniotic membrane, a new strategy of treating LSCD is to transplant a bio-engineered graft by expanding limbal SCs ex vivo. Herein, we conduct a critical appraisal of six protocols that have successfully been practiced in treating human patients with LSCD, and identify issues whether niche regulation has been disrupted or maintained during isolation and expansion. Consequently, we propose a future direction that may circumvent the potential pitfalls existing in these conventional protocols by preserving the interaction between limbal SCs and their native niche cells during isolation and expansion. Such an approach may one day help realize considerable promise held by adult SCs in treating a number of diseases.
角膜上皮的干细胞(SCs)位于角膜缘基底层,是维持角膜上皮内稳态的最终来源。与其他成人组织特异性SCs 一样,角膜缘SCs 的自我更新和命运决定受称为“龛位”的专门体内微环境调控。角膜缘SCs 的丧失或角膜缘龛位的功能障碍会导致角膜出现一种独特的临床疾病,称为角膜缘干细胞缺乏症(LSCD)。除了自体或同种异体角膜缘干细胞移植或羊膜移植外,治疗 LSCD 的新策略是通过体外扩增角膜缘SCs 移植生物工程移植物。在此,我们对已成功应用于治疗 LSCD 人类患者的六种方案进行了批判性评估,并确定了在分离和扩增过程中龛位调节是否被破坏或维持的问题。因此,我们提出了一个未来的方向,即在分离和扩增过程中保留角膜缘SCs 与其天然龛位细胞之间的相互作用,从而避免这些传统方案中存在的潜在陷阱。这种方法可能有一天有助于实现成人SCs 在治疗多种疾病方面的巨大潜力。