Therapeutic corneal stem cell delivery using hydrogels without the need for ex vivo expansion

角膜是我们通向世界的窗口，一旦受到伤害、疾病或年龄的损害，就会导致视力丧失。通过提供角膜干细胞移植的新方法，可以使更多的患者恢复视力。目前，角膜干细胞移植涉及一个漫长的术前步骤，在此期间，从供体眼睛中收集角膜干细胞，然后在移植前在烧瓶中培养以增加其数量。这一步耗时，技术要求高，而且非常昂贵，因为它需要训练有素的外科医生/科学家和专门的实验室。如果要充分实现角膜干细胞治疗的潜力，迫切需要开发具有成本效益的外科手术。这项研究源于我们之前的工作，即了解当前角膜干细胞移植技术的局限性，特别是用于生长和向患者输送干细胞的材料。在此之前，我们已经量化了角膜干细胞基质的纳米结构，并将这些测量结果应用于新型生物材料的设计。我们已经发现了一种凝胶基基质，它包裹着角膜干细胞，比目前的生物材料有显著的优势。因此，为了简化角膜干细胞移植，我们将开发一种基于凝胶的干细胞递送系统，该系统可以使用一系列接近人类的实验模型将相对少量的新鲜分离的角膜干细胞运输和保留到眼睛表面。这种凝胶会保留移植的干细胞足够长的时间，让它们附着、生长并修复受损的角膜。凝胶将超过90%的水（水凝胶），并具有与宿主组织非常相似的柔韧性程度。与其他形式的角膜干细胞移植不同，供体干细胞不需要长时间的培养。因此，移植材料的准备只需几分钟而不是几周即可完成，并且移植的细胞不会含有动物来源的生长因子或潜在危险的不需要的细胞类型（这两种情况都是干细胞在体外生长不可避免的后果）。可以刺激细胞生长的特定小分子也可以添加到凝胶中，以帮助替代异种物质。我们相信，将水凝胶应用于治疗性干细胞的输送也将适用于其他需要以非常精确的方式定位少量移植干细胞的病变组织（皮肤、骨骼、大脑、心脏）。

The cornea is our window to the world, once compromised by wounding, disease or age, a loss of vision results. By providing new methods of corneal stem cell transplantation the sight of many more patients can be restored. Currently, corneal stem cell transplantation involves a lengthy pre-surgical step during which time the corneal stem cells are harvested from donor eyes then grown in a flask to increase their number prior to transplantation. This step is time consuming, technically demanding and hugely expensive as it requires highly trained surgeons/scientists and specialized laboratories. If the potential for corneal stem cell therapy is to be fully realised cost effective surgical procedures need to be developed urgently. This investigation stems from our previous work in understanding the limitations of the current corneal stem cell transplantation techniques, specifically the materials used to grow and convey the stem cells to the patient. Previously, we have quantified the nanostructure of corneal stem cell substrates and applied these measurements to the design of new biomaterials. We have since discovered a gel-based substrate that encapsulates corneal stem cells has significant advantages over current biomaterials. Therefore, to simplify corneal stem cell transplantation we will develop a gel-based stem cell delivery system that can transport and retain a relatively small number of freshly isolated corneal stem cells to the surface of the eye using a range of experimental models that are close to humans. The gel will retain the transplanted stem cells long enough for them to attach, grow and repair the damaged cornea. The gel will be over 90% water (a hydrogel) and possess a degree of flexibility very similar to the host tissue. Unlike other forms of corneal stem cell transplant the donor stem cells will not require extended periods in culture. Therefore, preparation of the transplant material will take minutes not weeks to complete and the transplanted cells will not contain animal derived growth factors or potentially dangerous unwanted cell types (both unavoidable consequences of growing stem cells outside the body). Specific small molecules that can stimulate the cells to grow may also be added to the gel aiding the replacement of xenobiotic materials.We believe the application of hydrogels to the delivery of therapeutic stem cells will also be applicable to other diseased tissues (skin, bone, brain, heart) where there is a need to localise a small number of transplanted stem cells in a very precise manner.