TITLE:
Genetic Engineering of Surrogate β Cells for Treatment of Type 1 Diabetes Mellitus
AUTHORS:
Andrew M. Handorf, Hans W. Sollinger, Tausif Alam
KEYWORDS:
Gene Therapy, Cell Therapy, Insulin, Type 1 Diabetes Mellitus, Hepatocytes
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.5 No.4,
November
18,
2015
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.