MICA: Development of Metrics and Quality Standards for Scale up of Human Pluripotent Stem Cells

尽管世界各地的医学都取得了进步，但许多疾病仍然无法治愈。近年来，人们对使用人类多能干细胞(HPSCs)很感兴趣，hPSCs是一种未特化的细胞，可以使用发育中的身体中通常发现的分子来诱导产生任何类型的细胞。因此，这种干细胞可以用来为患有迄今无法治愈的不同疾病的患者制造特殊的修复组织，或者用于损伤后的受损组织。为了以我们的医疗系统负担得起的方式实现这一点，我们需要产生具有不同人类背景的干细胞库，这些干细胞库具有不同的免疫组织类型。然后，这些细胞就可以用来为患者量身定做所需的特殊细胞。然而，目前我们还没有可靠的方法来大量培养细胞，而不损害它们，或者改变它们的特性，使它们不能形成健康的组织。在这项提案中，我们将为大量产生健康的干细胞创造条件，同时保护它们免受破坏性影响。我们将生成一个适用于自动化细胞工厂的系统，这样细胞就可以在原始的无应力条件下进行监测和维护，并以稳定的方式进行扩张，从而为临床产生健康的组织。这样的系统是由东京电子公司开发的，该公司目前在英国设有基地。我们将评估这些hPSC的一系列不同特性，并找出这些细胞的哪些特性可以预测它们的健康状况和保持制造更多干细胞和形成特化细胞的能力。这些特性将与商业和其他替代的hPSC测试系统进行比较，并在第二阶段进行反馈，以进一步改善培养条件。在随后的第二阶段中，我们将在自动化细胞工厂中通过持续的细胞监测来试验改进的培养条件，以确定细胞标记的好坏。已建立的有效属性将提供给其他研究人员，以便他们可以使用它们来改进PSCs的扩展，并随后为不同的患者需求生成不同的专业细胞类型。

Many diseases remain untreatable in spite of advances in medicine world-wide. In recent years there has been much interest in using human pluripotent stem cells (hPSCs), unspecialised cells which can be coaxed using molecules that are found normally in the developing body to produce any cell type. Such stem cells can therefore be used to produce particular repair tissues for patients with different diseases that are so far incurable or for damaged tissues following injury. In order for this to be possible in a manner affordable to our healthcare systems, we need to generate banks of stem cells of different human background which have different immunological tissue types. These can then be used to make desired specialised cells tailored to the patient. However at the moment we do not have reliable ways to grow the cells in large numbers without damaging them, or changing their properties so that they cannot make healthy tissues. In this proposal we will develop the conditions for generating healthy stem cells in large numbers while protecting them from damaging influences. We will generate a system that will be suitable for an automated cell factory so that the cells can be monitored and maintained in pristine stress-free conditions and expanded in a stable way enabling them to in turn generate healthy tissues for the clinic. Such a system has been developed by a company, Tokyo Electron, which now has a base in the UK. We will evaluate a whole series of different properties of these hPSCs and work out which attributes of the cells predict their health and retention of the ability to make more stem cells and form specialised cells. These properies will be compared against commercial and other alternative hPSC test systems and, in the second phase, fed back to further improve culture conditions. In this subsequent second phase we will trial the improved culture conditions with continued cell monitoring for 'good' and 'bad' cell markers in the automated cell factory. The established validated properties will be made available to other researchers so that they can use them to improve their expansion of PSCs and subsequently generate different specialised cell types for different patient needs.