Stem cell derivation, differentiation and transplantation

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstract of Research


The goal of our programme is to establish ex vivo stem cell culture systems for eventual clinical application in tissue reconstitution and delivery of gene therapy. specifically we aim to acquire r, knowledge, understanding and methodologies that will enable development of human embryonic stem
as universal donors for cellular transplantation.


Three objectives central to any future clinical application will be pursued in parallel:

The derivation and propagation of non-transformed multipotential human stem cells analagous to mouse embryonic stem cells.


The generation from embryonic stem cells of neural cells with the capacity for long-term functional integration into the adult brain.


The engineering of transplantation compatibility in embryonic stem cells by modification and
substitution of regions of the genome.









<:f220,2Tms Rmn,0,0,0>Lay Summary


<:f160,2Tms Rmn,0,0,0>Many forms of illness or injury are associated with damage to and loss of particular types of cell.
7or example, in Parkinson‘s disease, which affects around 50,000 individuals in the UK, a specific
group of nerve cells die resulting in severe and progre5sive loss of motor control. If the wi3sing
cells could be replaced, the disease would be halted or even cured. Our research i3 concerned with
developing techniques that would allow cells grown in the laboratory to be used for such cell
replacement therapy.


<:f160,2Tms Rmn,0,0,0>The first requirement is to isolate and grow so-called stem cells. The early embryo contains a
population of stem cells that are responsible for growth and differentiation in the foetus. Such
cells are multipotential, that i3 they have the capacity to develop into a range of different
types of cell, for example blood cells and nerve cells. In mice it is possible to propagate these
stem cells as cell lines. We aim to establi5h similar stem cell lines from human embryos.


<:f160,2Tms Rmn,0,0,0>The second requirement is to determine the optimal conditions for successful transplantation. We
will focus on introduction of cells into the rodent brain. In particular we will examine the
potential of cell replacement to cure rodent model.5 of neurodegenerative di!3ease3-


<:f160,2Tms Rmn,0,0,0>The third component of the programme is to manipulate the stem cells in order to avoid rejection by
the ho5t immune system. Sophisticated genetic manipulations can be performed in the stem cells. It
should therefore be possible to substitute parts of the genetic constitution of the stem cell with
those of an individual patient. We aim to test this idea in mice and asse33 the impact on graft
rejection.









<+B><:f220,2Tms Rmn,0,0,0>1. 2


@2@<:f200,2Tms Rmn,0,0,0>flealth and Wealth Implications



<:f160,2Tms Rmn,0,0,0>Development of universal cellular transplant donors would potentially have eno=ous

<:f160,2Tms Rmn,0,0,0> cations for clinical practice. such <+!>cells <-!>could be used not only to treat
neL.-@degenerative di5ease but possibly for a range of tissue repairs, most obviously in
the lymphohaematopoietic reconstitution.


<:f160,2Tms Rmn,0,0,0>Stem cell transplantation would, in addition, provide a vehicle for delivery of gene
therapy.









<:f200,2Tms Rmn,0,0,0>12b. Planned Collaboration Details





<:f160,2Tms Rmn,0,0,0>Details of all collaborations are specified in the Plan of Investigation.


<:f160,2Tms Rmn,0,0,0>Letters of collaboration are appended.









<+B><:f200,2Tms Rmn,0,0,0>2.2