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，脐带在分娩后被丢弃为医疗废物。但是，在过去的几十年中，显然绳索包含少量的未成熟血细胞，具有强大的特性来修复人体。现在，经常使用脐带血，而不是骨髓来治疗儿童血液癌（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进行输血，或者如果处理不同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上试验，例如器官衰竭，儿童脑损伤或糖尿病等广泛的严重疾病。尽管自1990年代初以来，尽管全国脐带血收集和银行业计划，但这些新临床应用的成功将导致对已经紧张的脐带血库存的需求不可持续。在此奖学金中，我打算开发工具，以帮助从儿童出生时检索到的小样本中生产大量有价值的脐带血细胞。这将构成与生物相关的生物产品行业的基础。我们将在非常受控的条件下使用新技术在小容器中种植细胞。这些容器将使我们可以快速有效地测试不同的物理状况（例如氧和酸度）以及有关血细胞生长的新型化学添加剂。我们将采用工程方法以新颖的方式控制细胞的环境，并了解细胞开发之间的关系。我们将证明将这些细胞生长到大且临床上有用的数字所需的条件和系统。我们还将了解制造过程对重复生产安全有效细胞的耐受性。我提出的研究将帮助临床界为英国患者提供新的严重疾病治疗疗法，并帮助在英国开发重要的新经济活动，以开发这些新型基于细胞的疗法。

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

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

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

• 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

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