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

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.

Ex vivo control of proliferation and development of HSCs will create the opportunity for rapid clinical impact for patients suffering from haematological malignancies through a safe and unlimited supply of immunologically matched and consistent quality cells engineered to increase engraftment speed and decrease mortality. It will provide the scientific basis for a fully self-replenishing input cell supply for industrial production of naturally occurring haematopoietic lineages or haematopoietic cells engineered for therapeutic effect. This 'productisation' of cells will drive down costs for health service suppliers, create a manufacturing paradigm with sufficient economic return for product manufacturers, contribute to economic growth in a strategic area for the UK economy (high value bio-manufacturing), and create a UK technology based industry for export. It will bolster research into other therapeutic applications, such as organ support, through offering reproducible cells specifications for clinical trials. It will hasten the reality of manufactured cellular blood products and their manipulation for diverse therapeutic outcomes. The science developed will provide a powerful case study of the potential of interdisciplinary research and provide a pathway for other complex cell therapy developments with detrimental emergent parameters in bio-manufacture.