Pre-clinical development of a hematopoietic stem cell therapy product

许多患有血液疾病的患者，如癌症，通常可以通过接受另一个人的骨髓移植来治疗。通常情况下，捐赠者必须有血缘关系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。多年来，父母们一直在捐献在新生儿脐带中发现的血液。就像骨髓一样，这种“脐带血”含有干细胞，能够重建移植受者的整个血液和免疫系统。此外，完全匹配并不是必须的，因此脐带血可以用来治疗无法找到完全匹配的患者，从而降低组织排斥的风险。不幸的是，每个脐带血单位中的细胞数量有限，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。Platticell已经开发并申请了专利的配方，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增殖约500倍。该公司进一步开发了制造方法，使这些细胞可以扩展为临床使用。由此产生的细胞已经在实验室进行了体外测试，并使用免疫缺陷小鼠模型进行了初步的体内移植。然而，为了确保细胞对患者有用，我们必须进行更广泛的体内分析。在这个项目中，我们将测试注射到免疫缺陷小鼠体内的细胞重建整个血液系统的能力，并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、用户友好和负担得起的形式制造并交付给需要它的患者。

Many patients with blood disorders, such as cancers, can usually be 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 will test the cells ability to reconstitute the entire blood system when injected into immune-deficient mice and also aim to develop innovative solutions to ensure 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.