Scientists from The University of Manchester, in collaboration with
University of Sheffield researchers, genetically altered stem cells
to produce a larger number of pancreatic beta-cells, which have the
potential for producing insulin on in vivo transplantation. This new
approach could to be a promising step in developing novel therapeutic
strategies for diabetes.
Human embryonic stem cells (HESC) differentiate into different cell
lines corresponding to the three germ layers, and compared to this
diversity, the efficiency of producing a particular cell type is low.
Dr Karen Cosgrove, a research fellow and Faculty of Life Sciences at
The University of Manchester and colleagues, genetically manipulated
stem cells to overexpress the transcription factor Pax4, and analyzed
its role in the differentiation process using cell imaging and
various immunotechniques. Researchers found that Pax4 enhances the
differentiation of stem cells into pancreatic beta-cells. Isolation
of the cells with beta-cell markers was done with fluorescent-
activated cell sorting technique after staining with Newport Green
diacetate. Augmenting the differentiation of HESCs into beta-cells
through the overexpression of Pax4 transcription factor, could lead
to more number of insulin producing cells, thereby offering hope in
finding a new treatment modality for diabetes (especially type 1 and
in some type 2 diabetes that require insulin injections). This
technique, with its ability to provide an increased number of human
pancreatic cells, could also help in testing new drugs and disease
processes in diabetic patients.
Earlier studies have suggested pancreatic beta-cell replacement as an
alternative treatment for diabetes, as it may help in overcoming the
long-term adverse effects of the currently used conventional therapy.
Noguchi, et al. (Transplantation Proceedings, 2008) isolated
pancreatic stem cells from 8-week-old mice using a density gradient
purification method. Dithizone staining and handpicking under a
dissecting microscope were done to delete the islets from the layers.
They adopted the limiting dilution method to clone the remnant cells
after culturing and inoculation procedures. The induction medium
helped in the differentiation of pancreatic stem cells named as HN#5,
present in one of the wells, into insulin and albumin producing
cells. Based on the study, researchers suggested that this isolation
technique may aid in the identification and isolation of the human
progenitor cells of the pancreas.
Diabetes mellitus, a chronic disease, is characterized by
hyperglycemia due to low levels of hormone insulin secreted by the
beta-cells of the islets of Langerhans in the pancreas. Genetic and
environmental factors play a role in the etiology of diabetes, though
the exact cause is unknown. Polyuria, polydipsia, and unexplained
weight loss are the characteristic symptoms of diabetes. As of 2005,
20.8 million people, i.e., 7% of the population have diabetes in the
United States, with nearly one-third of them being unaware of their
disease condition. Some of the common complications of diabetes
include damage to the eyes, kidney and nerves, in addition to the
possibility of heart disease and stroke. As of now, there is no cure
for diabetes; however it can be managed by insulin therapy and oral
medications, depending on the type and extent of severity of the
disease.
Apart from embryonic stem cells, fetal and adult (cadaver) tissues
could also be a potent source for culturing islet cells, in the cell-
based therapy for diabetes. Several researchers are investigating the
use of these cells in reversing diabetes on animal models. However,
preliminary research suggests that the transplantation of embryonic
stem cells may lead to cancer in adults due its propensity for rapid
growth.
The novel approach for the enhancement of beta-cell differentiation
from the progenitor cells, using the transcription factor Pax4 could
be a major advancement in stem cell research for the treatment of
diabetes, with the need for further research to validate the study
results.
Reference
1. Stem cell breakthrough offers diabetes hope. Press Release. The
University of Manchester, England. Last accessed 8 April, 2008.
2. Noguchi H, Matsumoto S, Ueda M, et al. Method for isolation of
mouse pancreatic stem cells. Transplant Proc. 2008 Mar;40(2):422-
April 23rd, 2008 by The MediNEWS Team
http://www.medinews
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