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[S975]Stem Cells For Diabetes

by Wayne Channon, Way

Diabetes is a syndrome characterised by disordered metabolism and inappropriately high blood sugar resulting from either low levels of the hormone insulin or from abnormal resistance to insulin's effects coupled with inadequate levels of insulin secretion to compensate. The symptoms usually are excessive urine production, excessive thirst and increased fluid intake, and blurred vision; these symptoms are likely absent if the blood sugar is only mildly elevated.

The current best medical practice for those with type 1 diabetes includes insulin by multiple daily injections or continuous pump infusion. Recently developed insulin analogues have helped to more closely approximate normal glucose homeostasis and have been especially beneficial in reducing hypoglycaemia while tightly controlling blood glucose. Glargine insulin provides nearly 24 hours of low level basal insulin activity, while meal-time peaks in activity can be mimicked by administration of rapid acting insulin analogues such as lispro and aspart insulins. Delivery of insulin by continuous infusion pump allows even finer tuning of insulin activity.
Although current insulin delivery modalities are quite good and improving, limitations still exist. Frequent self-monitoring of blood glucose is still required, as is estimation of insulin doses based on multiple factors that might affect future glycaemic changes.

Stem cells offer a potential solution to the opposed requirements of cell proliferation and function. In theory, these cells can proliferate in an undifferentiated state and then be converted to take on required metabolic functions through genetic and epigenetic manipulations. Stem cells have been isolated from embryonic tissues as well as a variety of fetal and adult sources, including umbilical cord blood, bone marrow, central nervous system, liver and pancreas. One potential advantage of adult stem cells is that they could be used for autologous transplantation. This might preclude the use of immunosuppressive medications to prevent allorejection. However, recurrent autoimmune-mediated destruction targeting cell proteins would remain problematic.

Xenogeneic cells are a potential source of cells for transplantation therapy. Because pigs regulate glucose in a similar physiological range to that of humans, and because porcine insulin has been used as an exogenous source of insulin, pigs are generally considered the most promising donor animal. However, islets from xenogeneic pancreata are more immunogenic than allogeneic islets.

Achieving normal glycaemia is the goal of all diabetes therapy.

Potentially, there are many ways to achieve this goal, includingtransplantation of cells exhibiting glucose-responsive insulin secretion.However, to be applicable to the large number of people who might benefit fromstem cells replacement, an unlimited supply of stem cells must be found. Thosecells can then be stored by using a cord blood bank or stem cells bank.

To address this problem, cell lines from human endocrine pancreas havebeen developed.

In one case, a cell line has been developed from human islets that canbe induced under some circumstances to differentiate into functional stem cellsexhibiting appropriate glucose-responsive insulin secretion. Inducingdifferentiation is complex, requiring the activation of multiple signallingpathways, including those downstream of those involved in cell-cell contact andthe glucagon-like peptide receptor. In addition, transfer of the PDX gene isalso necessary to render the cells competent for differentiation. However, itis clear that many other genes are involved in maintaining the commitment ofstem cells towards the cell lineage. Understanding the complement of genesrequired to establish and maintain a stem cell lineage commitment would beenormously helpful in efforts to develop a cell line that can be used for stemcells replacement therapies.

Here, we provide further information on the characteristics of celllines that we have developed from the human pancreas that are relevant to thedevelopment of a stem cell replacement therapy for diabetes.

The recent explosion of interest in cell replacement therapies fordiabetes has been driven primarily by the dramatic progress in allogeneic isletcell transplantation. For the first time, the Edmonton group demonstrated that islettransplantation is a viable therapy for diabetes. This advance was dependentlargely on progress in immunosuppressive drug therapy that allowed for asteroid-free regimen. Further advances in this area are likely to result ineven better long term results as there is evidence that even the currentimproved drug regimens are toxic to stem cells, albeit to a lesser extent thanthe previous steroid containing regimens.

While the success of the Edmontontrial was an important proof of principle, it did not address the major problemwith islet transplantation, that is, the grossly inadequate supply of cadavericpancreas as a source of islets. Solving this problem has been a major focus ofresearch in stem cells biology.

Many different potential sources of cells for stem cells replacement,each with its own advantages and disadvantages, are being studied.

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Both Wayne Channon & Wayne are contributors for EditorialToday. The above articles have been edited for relevancy and timeliness. All write-ups, reviews, tips and guides published by EditorialToday.com and its partners or affiliates are for informational purposes only. They should not be used for any legal or any other type of advice. We do not endorse any author, contributor, writer or article posted by our team.

Wayne Channon has sinced written about articles on various topics from Stem Cell, Diabetes Treatment. Wayne Channon, Director of Cells4Life Ltd, a and expe. Wayne Channon's top article generates over 1300 views. to your Favourites.

Wayne has sinced written about articles on various topics from Supplements, Types of Cancer and Online Business. The author works for a and . They specialize in. Wayne's top article generates over 49500 views. to your Favourites.