Profiling patient-specific stem cells
Currently, much research is ongoing into the potential uses of stem
cells for treating or reversing aspects of MS disease. However these stem cells
are typically mature stem cells derived from bone marrow or fatty tissue, that
have limited capacity to specialise into other types of cells. In recent years,
research has created a new type of stem cell, which allows normal adult cells
to be reprogrammed into the earliest type of stem cell, known as induced
pluripotent stem cells (iPSCs), which are similar to cells found in a
Dr Natalie Payne, working with Professor Claude Bernard and his team at
Monash University, were the first group to derive iPSCs from people with MS.
They have since shown that these cells have the ability to specialise
(differentiate) into neural stem cells and the precursors of nerve cells. This
triggered an enormous global research effort, as these cells provide a unique
opportunity to study the unique aspects of the MS disease process in human
cells, as well as opening the door to understanding how stem cells might
contribute to repair and regeneration for people with MS.
Dr Payne received a MS Research Australia Incubator Grant in 2015,
supported by the Trish MS Research Foundation, to study iPSCs derived from
people with MS. Dr Payne’s project aimed to perform extensive molecular
profiling of these iPSC cells to understand more about the genes that are
expressed at each stage of development, and see how the developmental processes
differ between cells from people with MS and cells from healthy individuals.
This will provide clues into whether MS risk can be identified much earlier in individuals,
and help to differentiate between the roles of genes and the environment in the
development of MS.
In this project, Dr Payne studied skin cells from MS patients and their
unaffected siblings. The skin cells were converted into iPSCs, and these were
manipulated to develop into neural stem cells (the precursors of mature brain
cells) and mature nerve cells.
Dr Payne and colleagues performed extensive molecular profiling to
compare the original skin cells, the iPSCs, neural stem cells, and nerve cells
from people with MS and their healthy siblings. This was in order to identify
any differences in the structure or function of these cells that might be
relevant to the development of MS, or to their use in other applications such
as cell therapy. These analyses found that structurally these cells are all
very similar but the researchers found some important differences in genes that
are active at higher levels in neural stem cells compared to iPSCs, that may be
important for the development of MS. This molecular profiling has allowed the
researchers to identify some potential ways that stem cells may be used dampen
inflammation and promote repair in MS.
The solid results obtained during the course of this Incubator Grant
will underpin strong applications for further funding to pursue the therapeutic
potential of these stem cells and the team also plan to extend on these
findings by collaborating with international researchers who are also active in