Engineering Biological Science - Processes and Systems for Haematopoietic Stem Cell Based Therapy Manufacture

工程生物科学 - 造血干细胞疗法制造的流程和系统

• 批准号: EP/K00705X/1
• 负责人: Robert Thomas
• 金额: $ 164.94万
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK00705X%2F1
• 关键词: Engineering; Biological; Science; Processes; Systems

Umbilical cords are traditionally discarded after childbirth as medical waste. However, over the past few decades it has become apparent that the cord contains a small amount of immature blood cells with powerful properties to repair the human body. Cord blood is now frequently used instead of bone marrow to treat childhood blood cancers (leukaemia). Cord blood cells can also be grown to generate very large numbers of red blood cells or platelets for transfusion, or, if processed differently to create immune system cells. More recently cord blood has been proven effective, or is being clinically trialled, for a wide range of serious conditions such as organ failure, childhood brain damage or diabetes. Despite national cord blood collection and banking programmes since the early 1990's, the success of these new clinical applications will lead to unsustainable demand on already strained stocks of cord blood. In this Fellowship I intend to develop tools to help manufacture large quantities of medicinally valuable cord blood cells from the small samples retrieved at child birth. This will form the basis of a manufactured blood related bio-products industry.We will use a new technology to grow the cells in small vessels under very controlled conditions. These vessels will let us quickly and efficiently test different physical conditions (such as oxygen and acidity) and novel chemical additives on the growth of the blood cells. We will use engineering approaches to control the cells' environment in novel ways, and understand the relationships between the cells' development. We will demonstrate the conditions and systems that are necessary to grow these cells to large and clinically useful numbers. We will also understand how tolerant the manufacturing process is for repeated production of safe and effective cells. My proposed research will help the clinical community deliver a new cohort of treatments for serious diseases to patients in the UK as well as help develop an important new economic activity in the UK in the development of these new types of cell based therapies.

传统上，脐带在分娩后作为医疗废物被丢弃。然而，在过去的几十年里，人们已经发现脐带中含有少量未成熟的血细胞，这些血细胞具有强大的修复人体的功能。脐带血现在经常被用来代替骨髓来治疗儿童血癌（白血病）。脐带血细胞也可以生长以产生大量的红细胞或血小板用于输血，或者，如果以不同的方式处理以产生免疫系统细胞。最近，脐带血已被证明有效，或正在临床试验中，用于各种严重疾病，如器官衰竭，儿童脑损伤或糖尿病。尽管自20世纪90年代初以来，国家脐带血收集和储存计划，这些新的临床应用的成功将导致对已经紧张的脐带血库存的不可持续的需求。在这个奖学金中，我打算开发工具，帮助从婴儿出生时提取的小样本中制造大量具有医学价值的脐带血细胞。这将成为与血液相关的生物制品制造业的基础。我们将使用一种新技术，在严格控制的条件下，在小血管中培养细胞。这些血管将使我们能够快速有效地测试不同的物理条件（如氧气和酸度）和新的化学添加剂对血细胞生长的影响。我们将使用工程方法以新的方式控制细胞的环境，并了解细胞发育之间的关系。我们将展示这些细胞生长到大量临床有用数量所必需的条件和系统。我们还将了解制造过程对于重复生产安全有效的细胞的耐受性。我提出的研究将帮助临床社区为英国的患者提供新的严重疾病治疗方法，并帮助在英国开发这些新型细胞疗法的重要新经济活动。

项目成果

A mechanistic model of erythroblast growth inhibition providing a framework for optimisation of cell therapy manufacturing

• DOI: 10.1016/j.bej.2018.01.033
• 发表时间: 2018-05-15
• 期刊: BIOCHEMICAL ENGINEERING JOURNAL
• 影响因子: 3.9
• 作者: Glen, Katie E.;Cheeseman, Elizabeth A.;Thomas, Robert J.
• 通讯作者: Thomas, Robert J.

A quartz crystal resonator for cellular phenotyping

用于细胞表型分析的石英晶体谐振器

• DOI: 10.1016/j.biosx.2020.100057
• 发表时间: 2020
• 期刊: X
• 作者: Granja C

Human-Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient-Dependent Efficiency.

人类诱导的多能干细胞产生具有可变和养分依赖性效率的光响应性视网膜器官。

• DOI: 10.1002/stem.2883
• 发表时间: 2018-10
• 期刊: Stem cells (Dayton, Ohio)
• 作者: Hallam D;Hilgen G;Dorgau B;Zhu L;Yu M;Bojic S;Hewitt P;Schmitt M;Uteng M;Kustermann S;Steel D;Nicholds M;Thomas R;Treumann A;Porter A;Sernagor E;Armstrong L;Lako M
• 通讯作者: Lako M

Automated image analysis with the potential for process quality control applications in stem cell maintenance and differentiation.

• DOI: 10.1002/btpr.2199
• 发表时间: 2016-01
• 期刊: Biotechnology progress
• 影响因子: 2.9
• 作者: Smith D;Glen K;Thomas R
• 通讯作者: Thomas R

A Monte Carlo framework for managing biological variability in manufacture of autologous cell therapy from mesenchymal stromal cells therapies.

蒙特卡罗框架，用于管理间充质基质细胞疗法制造自体细胞疗法过程中的生物变异性。

• DOI: 10.1016/j.jcyt.2020.01.006
• 发表时间: 2020
• 期刊: Cytotherapy
• 影响因子: 4.5
• 作者: Picken A