Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine

生长因子是我们体内参与许多生理过程的分子，在发育过程中是关键的，因为它们控制着干细胞的功能。因此，这些分子具有在广泛的医疗条件下驱动组织再生的潜力，包括肌肉骨骼（骨修复）、血液学（骨髓移植）和心血管（梗塞、心脏病发作）疾病。生长因子目前是商业化生产的，并经常用于临床应用。然而，它们是非常强大的细胞信号分子，剂量至关重要，因为必须考虑到效果和安全性之间的平衡。到目前为止，在再生医学中使用生长因子只取得了部分成功，甚至存在争议。生长因子被迅速分解并被身体清除。这使得延长给药时间成为一个问题（这是修复所需要的），通常使用比所需剂量更高的剂量来解决这个问题。虽然它们对再生的帮助是毋庸置疑的，但附带的副作用可能是灾难性的，例如肿瘤的形成。我们已经开发了一种新技术，可以直接解决这些问题，因为它使用的材料（可以局部植入）可以提供低但有效的生长因子剂量；本课程是关于生长因子在临床应用中的安全使用。这不仅将降低目前接受生长因子治疗的患者的风险，而且将为更广泛的患者提供包括干细胞联合移植在内的治疗方法，因为医生不必在最迫切需要的情况下保留这些治疗方法。这种增加的使用将使成本最小化，因为生长因子非常昂贵，减少剂量将节省每次治疗的费用。我们的方法是独特的，这个项目资助将使我们能够通过创新的生物工程提高英国的世界领先地位。我们知道干细胞具有巨大的再生潜力，而生长因子提供了精细的干细胞控制——这两者目前都尚未开发。我们将设计新材料，使生长因子技术和关键的干细胞技术成为可能，在这些领域，传统方法远远达不到标准。

Growth factors are molecules within our body that participate in many physiological process that are key during development as they control stem cell function. These molecules thus have the potential to drive the regeneration of tissues in a broad range of medical conditions, including in musculoskeletal (bone repair), haematological (bone marrow transplantation) and cardiovascular (infarction, heart attack) diseases. Growth factors are currently produced commercially and are used regularly in clinical applications. However, they are very power cell signalling molecules and dose is critical as balance between effect and safety has to be considered. To date the use of growth factors in regenerative medicine has been only partially successful and even controversial. The growth factors are rapidly broken down and cleared by the body. This makes prolonged delivery (as is required to effect repair) a problem and typically higher than wanted doses are administered to get around this. While their help in regeneration is undoubted, collateral side effects can be catastrophic e.g. tumour formation. We have developed new technology that directly addresses these concerns as it uses materials (that can be topically implanted) to deliver low, but effective, growth factor doses; this programme is about the safe use of growth factors in clinical applications. This will not only reduce risks for patients who currently receive growth factor treatments, but will open up therapies that can include co-transplantation with stem cells to a wider range of patients as doctors would not have to keep these therapies back for cases of most pressing need. This increased use would minimise costs as growth factors are very expensive and reduced dose would save money per treatment. Our approach is unique and this programme grant will allow us to enhance the UK's world leading position through innovative bioengineering. We know that stem cells have huge regenerative potential and that growth factors provide exquisite stem cell control - both are currently untapped. We will engineer new materials to enable growth factor technology, and critically stem cell technologies, where traditional approaches are falling very short of the mark.