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

使用水凝胶进行治疗性角膜干细胞递送，无需离体扩增

• 批准号: G0900877/1
• 负责人: Che Connon
• 金额: $ 56.5万
• 依托单位: University of Reading
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900877%2F1
• 关键词: Therapeutic; corneal; stem; cell; delivery

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.

角膜是我们通往世界的窗口，曾经因受伤，疾病或年龄而遭受损害的视力丧失。通过提供新的角膜干细胞移植方法，可以恢复更多患者的视线。目前，角膜干细胞的移植涉及一个漫长的术前步骤，在此期间，从供体眼中收获角膜干细胞，然后在烧瓶中生长以在移植前增加数量。此步骤是耗时，技术要求和昂贵的，因为它需要训练有素的外科医生/科学家和专业实验室。如果要充分实现角膜干细胞疗法的潜力，则需要紧急开发具有成本效益的手术程序。这项研究源于我们以前在了解当前角膜干细胞移植技术的局限性方面的工作，特别是用于生长和将干细胞传达给患者的材料。以前，我们已经量化了角膜干细胞底物的纳米结构，并将这些测量应用于新生物材料的设计。此后，我们发现了一种基于凝胶的底物，该基材封装了角膜干细胞比当前的生物材料具有显着的优势。因此，为了简化角膜干细胞的移植，我们将开发一个基于凝胶的干细胞输送系统，该系统可以使用一系列接近的实验模型将相对较少数量的新鲜角膜干细胞运输到眼睛表面的较小新鲜分离的角膜干细胞。人类。凝胶将保留移植的干细胞足够长的时间，以使其附着，生长和修复受损的角膜。凝胶将超过90％的水（水凝胶），并且具有与宿主组织非常相似的柔韧性。与其他形式的角膜干细胞移植不同，供体干细胞不需要延长培养时间。因此，移植材料的制备将需要几分钟的时间才能完成，并且移植细胞将不包含动物衍生的生长因子或潜在危险的不良细胞类型（这两种不可避免的后果都无法避免体内生长的干细胞）。可能刺激细胞生长的特定小分子也可以添加到凝胶中，以帮助替换异生物生物材料。我们相信，将水凝胶应用于治疗干细胞的递送也将适用于其他患病的组织（皮肤，骨骼，骨骼，骨骼，骨骼，骨骼，骨骼，骨骼，大脑，心脏）需要非常精确的方式来定位少量移植干细胞。