Finally, appropriate b-cells and successfully be transplanted

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we are very close to finding a cure for type 1 diabetes. Stem cells have the
capability to just that, and even more. There is potential for them to treat type
1 diabetes and improve the lives of those with type 2. Stem cells will continue
to improve with other technology eventually leading up to being able to
differentiate into appropriate b-cells and successfully be transplanted and
working in those who require it. Stem cells are currently considered a frontier
for diabetes therapy, but it could eventually develop to become its basis.

previous research stated by Millman et. al (2015) seems to share similar ideas
and finding to another research done a few years earlier. This research by
Maehr et. al (2009) shows that using human induced pluripotent stem cells is
better than embryonic because they have been generated as a tool for human
disease modeling. Embryonic stem cells only model diseases that can be diagnosed
or predicted by Mendelian genetics. Type 1 diabetes is a disease with complex underlying
genetics and unidentified environmental triggers. Cell replacement therapy
would require a source of glucose-responsive, insulin secreting cells. In
theory, mouse and human fibroblasts would be used to generate induced
pluripotent stem cells. The T1D- specific induced pluripotent (DiPS) cells
would contain the genotype for the disease for further studies. The purpose of
this study was to derive DiPS cells from patients with type 1 diabetes and
determine whether or not the cells can be differentiated into the pancreatic
b-cell. Observing the stem cells, b-cells derived from DiPS are glucose responsive,
but is not yet possible to directly compare them with purified pancreatic
b-cells until differentiation protocols have improved. “In addition to variation in differentiation propensities, potential
deviations in T1D disease onset and progression will require the generation of
multiple DiPS lines to reflect the human population afflicted with T1D” (Maehr
et. al, 2009). It is said that T1D is not exactly the same in everyone who has
it. But, it is concluded that DiPS cells can be differentiated to insulin producing/glucose-responsive
cells. Differentiation of DiPS cells to b-cells is important for the long-term
possibility of autologous (obtained from same organism) cell replacement therapy
and also for disease modeling (Maehr et. al, 2009).

            After several more months of observations following the
transplantation, the grafts continued to respond to glucose injections, and
high amounts of human insulin were detected. The SC-b cells were also able to
maintain euglycemia (normal concentration of glucose in the blood) after the
destruction of the all mouse b-cells. The SC-b cells continued to secrete human
insulin in response to glucose injections, and rapidly clear glucose as well.
This data shows the efficiency of continued function for more than five months in vivo (taking place in a living organism).
In conclusion of this research, T1D SC-b cell function is very similar to ND
SC-b cell function both in vitro and in vivo (Millman et. al, 2016). These
results present the possibility of using the T1D SC-b cells as successful
treatment of diabetes, further study b-cell biology, and stem cells.

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            Generating stem cell derived b-cells (SC-b cell) from T1D
patients was the first step in the process of finding a potential cure for
diabetes. This was done by deriving and characterizing human induced
pluripotent stem cells from skin fibroblasts (cells that generate connective
tissue) of patient donors. The cells were then adapted to suspension culture to
undergo differentiation to produce SC-b cells. T1D SC-b cells increased insulin
secretion in response to many anti-diabetic drugs. It is also shown that those
cells respond to different types of chemically induced stress. A treatment of a
small molecule was used to partially rescue this stress phenotype. In doing so,
an in vitro (taking place outside of
any living organism) disease model of T1D SC- b cell stress was developed. “To evaluate their
potential use in cell replacement therapy and in vivo physiological
tests and further confirm their identity as SC-? cells, T1D and ND SC-? cells
were transplanted underneath the kidney capsule of ND immunocompromised mice”
(Millman et. al, 2016). To test transplantation of the stem cells and further
responses after, both T1D and ND SC-b cells were transplanted into mice. Their
responses to certain tests were observed and compared to determine similarities.
Measuring human insulin to evaluate graft function before and after a glucose
injection of the mice presented the first set of results of the stem cells. Human
insulin was detected and the grafts were glucose responsive in most of the
mice. In the T1D SC-b cell mice, 81% secreted more insulin after the glucose
injection, The ND SC-b cells mice had 77% secrete more insulin. Therefore, no
major differences between the two cells were actually observed (Millman et. al,

            Human embryonic stem cells have the capability to
differentiate into any cell type. With damage caused at one particular cell
type, type 1 diabetes is a good candidate for stem cell therapy. Around 5-10%
of diabetes cases are type 1 (“Diabetes,” n.d.). Unfortunately, it is difficult
to study it in human patients because once it is diagnosed, destruction of the
b-cells is nearly complete with no way to discover what caused the immune
system to attack them in the first place. Furthermore, stem cells could
possibly differentiate into b-cells while responding to molecular signals in
the pancreatic environment, which would eventually be introduced into the body.
They would migrate to the damaged tissue and further differentiate to maintain
b-cell mass. Stem cell therapy would benefit those with type 1 by replenishing
those b-cells that were destroyed by the autoimmune processes. This method
could eventually be beneficial for those with type 2 diabetes as the failing
b-cells caused by the disease could be replaced, which is one step closer to a
cure. Overall, type 1 diabetes stem cells can be used to further study diabetes
and cell replacement therapy (Goldthwaite, 2016).

Diabetes affects around
250 million people worldwide and is the sixth leading cause of death in the United
States. There are two types of diabetes: Type 1 (T1D) and Type 2 (T2D). Type 1
diabetes develops when the body’s immune system deviates from its normal role
and destroys the insulin-producing beta cells (b-cells) of the pancreas. Type 2
diabetes is more common but can be more preventable than type 1. It is
characterized by two things: insulin resistance and subsequent progressive
decline in b-cell function. Insulin resistance is a condition in which tissues
in the body no longer respond to insulin action. The decline in b-cell function
continues to the point that the cells no longer produce enough insulin to
overcome the insulin resistance. Diabetes may lead to other complications in
the body including increased risk for heart disease, stroke, kidney disease,
blindness, and amputations. At the moment, there is no cure, diabetes can only
be managed. But with new technology such as embryonic or induced pluripotent stem
cells, there is a possibility to cure at the least, Type 1 diabetes
(Goldthwaite, 2016).

Categories: Biology


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