Genetic Engineering of Surrogate β Cells for Treatment of Type 1 Diabetes Mellitus - Journal of Diabetes Mellitus

JDM > Vol.5 No.4, November 2015

Genetic Engineering of Surrogate β Cells for Treatment of Type 1 Diabetes Mellitus ()

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Download as PDF (Size: 840KB) PP. 295-312

DOI: 10.4236/jdm.2015.54037 5,472 Downloads 7,920 Views Citations

Author(s)

Andrew M. Handorf, Hans W. Sollinger^*, Tausif Alam

Affiliation(s)

Department of Surgery, Division of Transplantation, University of Wisconsin-Madison, Madison, USA.

ABSTRACT

Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from the destruction of the insulin-producing β cells of the pancreas. While treatment options like daily insulin injections or transplantation of whole-pancreas exist, they are associated with significant drawbacks. As a result, there has been great interest in engineering surrogate β cells, both ex vivo and in situ, to replace the function of those cells lost during the progression of the disease. However, the β cell is highly specialized and extraordinarily adept at synthesizing and rapidly secreting the appropriate amount of insulin in response to even small increases in blood glucose levels. Thus, genetic engineering of the “perfect” β cell may prove impossible. In this review, we will detail the features of β cells that make them so proficient at regulating blood glucose and highlight the key features that absolutely must be met by surrogate β cells if they are to be suitable for treatment of T1DM. Then, we will summarize the current approaches used to genetically engineer surrogate β cells, including the overexpression of β cell-specific transcription factors and insulin gene therapy. Along the way, we will discuss the advantages and disadvantages of each approach and review important studies in the field. Lastly, we will discuss important future directions necessary to genetically engineer surrogate β cells with the potential to treat T1DM.

KEYWORDS

Gene Therapy, Cell Therapy, Insulin, Type 1 Diabetes Mellitus, Hepatocytes

Share and Cite:

Handorf, A. , Sollinger, H. and Alam, T. (2015) Genetic Engineering of Surrogate β Cells for Treatment of Type 1 Diabetes Mellitus. Journal of Diabetes Mellitus, 5, 295-312. doi: 10.4236/jdm.2015.54037.

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