Critical issues for engineering cord blood stem cells to produce insulin.
OBJECTIVE
The objectives of using cord blood stem cells for treating type 1 diabetes are simple in principle yet complex in biological and molecular mechanisms. These are defined by the complexity of the insulin-producing unit of the pancreas, the islet. Islets are composed of various cell types that arise from diverse lineages and communicate by hormones, growth factors and small-molecule mediators. These processes are regulated by integration of signal transduction pathways. While advances have been made to engineer umbilical cord blood stem cells to produce insulin, these studies only illuminate the potential of such cells to fulfil a necessary, but not sufficient, requirement for transplantation.


CONCLUSIONS
The challenges ahead demand detailed understanding of molecular mechanisms to move from an opportunistic, phenotypic approach to transplantation and amelioration of blood glucose, to an orderly and logical approach to a biologically and medically meaningful solution. The issues include expansion to generate large numbers of cells, self-renewal to regulate the destiny of cord blood stem cells to repopulate the hematopoietic system, and multipotency of stem cells to generate the distinct cell types of an islet.
Denner
Larry
L
Urban
Randall J
RJ
D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D005312:Fetal Blood / Q000166:cytology*; D005818:Genetic Engineering; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D013234:Stem Cells / Q000378:metabolism*
D007328:Insulin