Engineered advances for clinical applications of gene therapy

血细胞的产生是一个复杂的多步骤过程，起源于一种罕见的自我维持干细胞亚群。血细胞生产的显著中断激活这些干细胞并刺激它们再生系统。大多数造血干细胞通常存在于骨髓中，但它们也会自发进入血液，然后返回骨髓。造血干细胞的潜在再生活性与其在静脉注射后有效地重新回到骨髓的能力相结合，是目前全球临床使用的骨髓移植疗法的基础。这种方法的一个强大的应用是从患有遗传疾病的患者身上收集干细胞，“离体”纠正缺陷，然后尝试通过移植他们自己的纠正后的干细胞来治愈患者。这种基于干细胞的基因治疗策略为许多患有先天性疾病的患者提供了巨大的益处，如6-地中海贫血和镰状细胞病-这两种遗传性疾病对世界各地数百万人的生活产生了不利影响。然而，重大障碍继续阻止基于干细胞的基因疗法成为实际的临床程序。血液干细胞的转导效率非常低，而且一旦置于培养物中，它们也会迅速分化。为了解决这些问题，一个由生物过程工程师和干细胞医学研究人员组成的独特团队将评估并提出他们最近发现的能够在模型系统中规避这些问题的几种新型试剂。因此，该项目的成功将大大提高永久治愈各种血液疾病患者的可能性，这些疾病困扰着成千上万的加拿大人及其家庭，目前除了姑息治疗外，没有已知的替代方法。

Blood cell production is a complex multi-step process that originates in a rare subpopulation of self-maintaining stem cells. Significant interruption of blood cell production activates these stem cells and stimulates them to regenerate the system. Most of the blood stem cells normally reside in the bone marrow, but they do also spontaneously enter the blood stream and then return to the bone marrow. The latent regenerative activity of blood stem cells in combination with their ability to efficiently re-home to the bone marrow following intravenous injection are the basis of bone marrow transplant therapies now in clinical use worldwide. A powerful application of this approach is to harvest stem cells from patients with genetic disorders, correct the defect "ex vivo" and then attempt to cure the patients by transplanting them with their own, corrected stem cells. This type of stem cell-based gene therapy strategy offers the potential of enormous benefit to many patients with congenital disorders like 6-thalassemia and sickle cell disease - 2 inherited diseases that adversely affect the lives of millions of people around the world. However, significant hurdles continue to prevent stem cell-based gene therapies from becoming a practical clinical procedure. Blood stem cells are transduced very inefficiently and they also differentiate rapidly as soon as they are placed in culture. To address these issues, a unique team of bioprocess engineers and stem cell medical researchers will evaluate and bring forward several novel reagents they have recently identified as able to circumvent these problems in model systems. The success of this project will thus greatly advance the possibility of permanent cures for patients with a wide variety of blood disorders that afflict thousands of Canadians and their families, and for which there are currently no known alternatives beyond palliative treatments.