DEVELOPMENT OF A NON-INVASIVE STRATEGY ENHANCING HAEMATOPOIETIC STEM CELL (HSC) POTENTIAL OF HUMAN UMBILICAL CORD CELLS

含有血液干细胞的骨髓移植被称为造血干细胞(HSC)，几十年来一直被用于各种血液疾病的有效治疗。然而，由于缺乏合适的捐赠者，这种治疗方法的使用受到限制。寻找高效生产造血干细胞的方法或富含造血干细胞的替代来源是当前血液学的主要目标之一。脐带血是一种很容易获得的潜在的非常重要的造血干细胞来源，但那里包含的造血干细胞数量很少，这限制了它在成人治疗中的使用。这个项目的目的是在我们实验室以前开发的基础上开发一种方法，使脐带的HSC活性得到显着增强。HSCs是在胚胎发育过程中高效产生的，我们之前已经在发育中的胚胎中发现了HSCs的一个强大来源，现在被称为AGM区。我们开发了一种新的技术，使我们能够从培养的AGM区域产生大量的HSC。在这里，我们建议使用AGM细胞来增强脐带HSC的活性。我们将AGM区的细胞与人脐带细胞群进行共培养。为了使这一方法标准化，并使其与临床环境兼容，我们将从人类AGM区域提取永生化细胞系，并测试它们对脐带细胞的诱导能力。我们将通过使用移植的金标准测试来评估从脐带产生造血干细胞的情况，在移植中，人类血细胞的长期植入将在受者动物身上进行评估。

Transplantations of bone marrow containing blood stem cells termed haematopoietic stem cells (HSC) have been used for several decades for efficient treatment of various blood diseases. However, due to shortage of appropriate donors, the use of this treatment is limited. Search for methods of efficient production of HSCs or alternative sources enriched for HSCs is one of the key goals of current haematology. Umbilical cord (UC) blood is an easily accessible and potentially very important source of HSCs but the number of HSCs contained there is low, which limits its use for treatment of adults. The aim of this project is to develop a methodology based on previous development in our laboratory which would allow significant enhancement of HSC activity of the umbilical cord. HSCs are efficiently generated during embryonic development and we have previously identified a powerful source of HSCs in the developing embryo, now termed the AGM region. We have developed a novel technique, which allowed us to generate large numbers of HSCs from the AGM region in culture. Here we propose to use the AGM cells for enhancement of the HSC activity of the umbilical cord. We will co-culture cells from the AGM region with cell populations of human umbilical cord cells. To standardise this approach and also to make it compatible with clinical settings we will derive immortalised cell lines from the human AGM region and test their inductive capacity on umbilical cord cells. We will assess the production of HSCs from the umbilical cord by the gold standard test using transplantations in which long-term engraftment of human blood cells will be assessed in recipient animals.