Resilience Fund (Strand 2) application for project 133873 “Pre-clinical development of a hematopoietic stem cell therapy product”

许多血液疾病患者，如癌症，通常通过接受他人的骨髓移植来治疗。通常，捐赠者必须是血亲或有相容的组织类型，以确保移植不会被排斥。然而，找到这样的匹配并不总是可能的。几年来，父母们一直在捐献新生儿脐带中的血液。就像骨髓一样，这种“脐带血”含有干细胞，能够重建移植接受者的整个血液和免疫系统。此外，脐带血不需要完全匹配，因此脐带血细胞可以用于治疗无法找到完全匹配的患者，降低组织排斥的风险。不幸的是，每个脐带血单位的细胞数量有限，而且太小，无法治疗大多数成年人，因此，在实验室中扩大这些细胞数量的方法是非常可取的。Plasticell已经开发并获得专利的配方，在初步的体外研究中，允许脐带血单位中的干细胞在不影响其特性的情况下繁殖约500倍。该公司已经进一步开发了制造方法，使这些细胞可以扩展为临床使用。所得到的细胞已经在实验室进行了体外试验，并在免疫缺陷小鼠模型上进行了初步的体内移植试验。然而，为了确保这些细胞对病人有用，我们必须进行更广泛的体内分析。在这个项目中，我们正在测试将扩增的脐带血细胞注射到免疫缺陷小鼠体内后重建整个血液系统的能力。我们还致力于开发创新的解决方案，以确保我们正在开发的干细胞产品能够以安全、有效、用户友好且负担得起的形式生产并交付给需要的患者。

Many patients with blood disorders, such as cancers, are often treated by receiving a bone marrow transplant from another person. Usually, this donor has to be a blood relation or have a compatible tissue type to ensure the transplant is not rejected. However, finding such a match is not always possible. For some years now, parents have been donating the blood found in the umbilical cord of their new-born babies. Just as with bone marrow, this 'cord blood' contains stem cells which are capable of reconstituting the entire blood and immune system of a transplant recipient. Furthermore, complete matching is not required, so cord blood cells can be used to treat patients that can't find exact matches, lowering the risk of tissue rejection. Unfortunately, the number of cells in each cord blood unit is limited and too small to treat most adults, therefore methods to expand the number of these cells in the laboratory are highly desirable. Plasticell has developed and patented formulations which, in preliminary _in vitro_ studies, allow the stem cells in the cord blood units to be multiplied by around 500-fold without affecting their properties. The company has further developed manufacturing methods in which these cells can be expanded ready for clinical use. The resulting cells have been tested _in vitro_ in the laboratory and in preliminary _in vivo_ transplantation using immune-deficient mouse models. Nevertheless, to ensure the cells are useful to patients we must carry out more extensive _in vivo_ analyses. In this project, we are testing the ability of expanded cord blood cells to reconstitute the entire blood system when they are injected into immune-deficient mice. We also aim to develop innovative solutions to ensure that the stem cell product we are developing can be made and delivered to the patients that need it in a format that is safe, effective, user-friendly and affordable.