Cellular & Molecular Medicine: Open access

Type 1 diabetes mellitus (T1DM) results from auto-immune destruction of the insulin secreting β-cells of the pancreas

Type  1  diabetes  mellitus  (T1DM)  results  from  auto-immune  destruction  of  the  insulin secreting  β-cells  of  the  pancreas.  The  most  common  treatment  is  injection  of  exogenous insulin,  but  this  allows only partial control over blood glucose levels, so other therapies are needed.  Pancreatic  islet  transplantation  has  shown  proof  of  principle  for  cell  replacement therapy  to  treat  T1DM. There are several sources of cells which could be used, but much of the  focus  has  been  on  pluripotent  stem  cells,  which  are  able  to  self-renew  indefinitely  in culture  and  give  rise to any cell in the body. Insulin-expressing cells have successfully been produced  from  embryonic  stem  cells  (ESCs)  by  recapitulating  embryonic  development  in vitro. 
However, problems associated with the use of ESCs  mean that an alternative cell source is needed.  In 2006, it was discovered that 4 transcription factors can reprogram somatic cells into   induced   pluripotent   stem   cells   (iPSCs).   iPSCs   provide   an   alternative   source   of pluripotent  stem  cells  and  can  be  derived  in  a  patient-specific  manner.  iPSCs  have  been shown to differentiate in vitro into insulin-expressing cells, but it is unknown whether iPSCs are truly equivalent to ESCs. Important differences have been shown to exist between iPSCs and ESCs which may affect the ability of iPSCs to give rise to cells of a pancreatic lineage and therefore limit their usefulness for the treatment of T1DM. 
The  aim  of  this  problem  is  to  identify  whether  iPSCs  are  a  viable  alternative  to  ESCs  for generating   β-cells   in   vitro   for  cell  replacement  therapy  to  treat  type  1  diabetes.  The differentiation potential of iPSCs and ESCs to give rise to first definitive endoderm (the first stage  in  differentiation  towards  a  pancreatic  lineage)  in  vitro  will  be  compared,  and  the involvement of miRNAs in differentiation of ESCs and iPSCs to definitive endoderm will be investigated.
 

Author(s):

Darryl Amadeo

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