A Cure for Type 1 Diabetes? Not Yet, but We Can Get Closer
Type 1 diabetes (T1D) is an autoimmune disease in which the body’s immune system mistakenly attacks the insulin-producing beta cells within the pancreas. Insulin is a hormone required for the cells to utilise glucose, a type of sugar that comes from the foods we eat, to enter the cells as a major energy source. People with T1D have glucose built up in their bloodstream, which can lead to a variety of issues. Poor management of T1D can result in developing eye problems, heart disease, kidney diseases and nerve damage. The only treatment available widely is the ongoing injection of insulin, which is onerous and imprecise. However, pancreas transplantation as an experimental treatment now shows a promising potential to become a revolutionary strategy to treat T1D, or even turn out to be a cure. The success of pancreas transplantation is defined by insulin independence, which means the body is able to make proper amount of insulin in response to blood sugar levels.
The implication of islet transplantation as routine therapy in clinics is hampered by the scarcity of sources, which relies on donations from deceased donors. Meanwhile, the quality of the transplantation materials is inconsistent. The current procedure of transplantation only includes a rough test for assessing the purity of the transplantation material. Notably, beta cells are resided along with a range of other cells in a region of the pancreas called pancreatic islets. Whereas many studies demonstrated that the composition of transplanted islets critically affects the outcome of transplantation, a time-efficient technique for characterising the quality and composition of islets prior to transplantation is still lacking. To fill some of the gaps, our project is aiming to construct a robust method to examine the pre-transplantation materials either from the donated pancreas or stem cell-derived pancreas.
Protein molecules presenting on the cell surface serve as useful markers. Our research groups have identified a cohort of markers for important hormone-secreting cells within the human pancreatic islets via single-cell RNA sequencing. A unique set of markers allows us to generate an expression profile for each cell. Expression profiles basically function like the photo ID for cells, which contain enough characteristic information for us to identify their cell types. In this project, a novel set of high-quality antibodies will be generated for assessing the composition of transplanted material by fluorescence imaging (IF) and fluorescence-activated cell sorting (FACS). IF provides a quick check of cell composition through visualisation. It relies on fluorescence dyes bound to cell surface markers that specifically presenting on certain cell types in the pancreas. FACS can quantify the abundance of specific cell types in a sample, provided suitable markers. Following the assessment of the pre-transplantation material, we are aiming to figure out the correlation between the composition of transplanted islets and the post-transplantation outcomes.
This project will address a gap in the field of islet transplantation, namely the current lack of pre-transplantation characterisation. Such scorecards will improve the methodology currently used in islet transplantation therapy and provide benchmarking strategy that enables direct selection of the transplantation sources. Furthermore, it will provide new knowledge about the hormone-secreting cells within the human pancreas, and it may be useful for predicting cellular functions. Last, it may assist our work in generating mature and functional insulin-secreting cells from stem cells. It puts us closer to achieving full blood sugar control without lifelong insulin injections, which is the ultimate goal of treatment or finally a so-called “cure” for T1D.
A Cure for
Type
1 Diabetes? Not
Yet
,
but
We Can
Get
Closer
Type 1 diabetes (T1D) is an autoimmune disease in which the body’s immune system
mistakenly
attacks the insulin-producing beta
cells
within the pancreas. Insulin is a hormone required for the
cells
to
utilise
glucose, a
type
of sugar that
comes
from the foods we eat, to enter the
cells
as a major energy source.
People
with T1D have glucose built up in their bloodstream, which can lead to a variety of issues. Poor management of T1D can result in developing eye problems, heart disease, kidney diseases and nerve damage. The
only
treatment available
widely
is the ongoing injection of insulin, which is onerous and imprecise.
However
, pancreas transplantation as an experimental treatment
now
shows
a promising potential to become a revolutionary strategy to treat T1D, or even turn out to be a cure. The success of pancreas transplantation
is defined
by insulin independence, which means the body is able to
make
proper amount of insulin in response to blood sugar levels.
The implication of
islet
transplantation as routine therapy in clinics
is hampered
by the scarcity of sources, which relies on donations from deceased donors. Meanwhile, the quality of the transplantation
materials
is inconsistent. The
current
procedure of transplantation
only
includes a rough
test
for assessing the purity of the transplantation
material
.
Notably
, beta
cells
are resided
along with a range of other
cells
in a region of the pancreas called pancreatic islets. Whereas
many
studies demonstrated that the
composition
of transplanted islets
critically
affects the outcome of transplantation, a time-efficient technique for
characterising
the quality and
composition
of islets prior to transplantation is
still
lacking. To fill
some of the
gaps, our project is aiming to construct a robust method to examine the pre-transplantation
materials
either from the donated pancreas or stem cell-derived pancreas.
Protein molecules presenting on the
cell
surface serve as useful markers. Our research groups have identified a cohort of markers for
important
hormone-secreting
cells
within the human pancreatic islets via single-cell RNA sequencing. A unique set of markers
allows
us to generate an expression profile for each
cell
. Expression profiles
basically
function like the photo ID for
cells
, which contain
enough
characteristic information for us to identify their
cell
types
. In this project, a novel set of high-quality antibodies will
be generated
for assessing the
composition
of transplanted
material
by fluorescence imaging (IF) and fluorescence-activated
cell
sorting (FACS). IF provides a quick
check
of
cell
composition
through
visualisation
. It relies on fluorescence dyes bound to
cell
surface markers that
specifically
presenting on certain
cell
types
in the pancreas. FACS can quantify the abundance of specific
cell
types
in a sample, provided suitable markers. Following the assessment of the pre-transplantation
material
, we are aiming to figure out the correlation between the
composition
of transplanted islets and the post-transplantation outcomes.
This project will address a gap in the field of
islet
transplantation,
namely
the
current
lack of pre-transplantation
characterisation
. Such scorecards will
improve
the methodology
currently
used
in
islet
transplantation therapy and provide benchmarking strategy that enables direct selection of the transplantation sources.
Furthermore
, it will provide new knowledge about the hormone-secreting
cells
within the human pancreas, and it may be useful for predicting cellular functions. Last, it may assist our work in generating mature and functional insulin-secreting
cells
from stem
cells
. It puts us closer to achieving full blood sugar control without lifelong insulin injections, which is the ultimate goal of treatment or
finally
a
so
-called “cure” for T1D.