Biomedical Engineering Reference
In-Depth Information
nonmyeloablative hematopoietic stem cell transplantation in 15 patients with
newly diagnosed type 1 diabetes. This treatment was combined with cyclophos-
phamide and rabbit antithymocyte globulin to reset the immune system memory
and allow for the endogenous regeneration to take place. In this study 14 out of 15
patients achieved an insulin-free state for variable periods of time.
The umbilical cord blood (UCB) contains an immunomodulatory and regen-
erative potential because of its stem cell and regulatory T cell content [
103
].
Treatment with human umbilical cord blood cells improved glycemia in both type
1 and type 2 diabetic mouse models and also improved the diabetes-associated
nephropathy and neuropathy [
104
,
105
]. Considering this beneficial effect, Haller
et al. [
106
] carried out autologous UCB transfusion in seven children with recent-
onset type 1 diabetes. A 6-month follow-up showed reduced insulin requirement
and lowered HbA1c levels; however, no patient became insulin-free.
GABA (c-aminobutyric acid) is the major inhibitory neurotransmitter in the
central nervous system. However, the GABAergic system has been identified in
many of the non-neuronal tissues as well including the pancreas, suggesting its
role in those tissues [
107
]. Recently, Soltani et al. [
108
] demonstrated that GABA
treatment can preserve the b cell mass by activating a survival pathway in b cells
and at the same time reduce inflammatory cytokine production. In diabetic mice,
GABA treatment restored b cell mass and reversed hyperglycemia. Considering
the b cell protective and immunoinhibitory effect of GABA, it may prove to be a
potential candidate for the treatment of type 1 diabetes. If successful, GABA-based
therapy would be much easier to utilize because GABA as a dietary supplement
already exists.
9.5 In Vitro Differentiation and Expansion of b Cells
As mentioned in the first section, one of the main obstacles in the b cell
replacement therapy is the shortage of available material, i.e., whole pancreas or
islets. While one part of the regenerative research is focused on the promotion of
endogenous b cell regeneration, the other part is related to the generation of b cells
or islet-like structures in vitro, which can then be transplanted instead of the real
donor islets. In order to replace the real donor islets such ex vivo generated
endocrine cells should be functionally mature which means that they are able to
secrete insulin after glucose stimulation and at a level that is physiologically
acceptable. In this section, the sources and possible strategies involved in the ex
vivo generation of b cells are briefly described.
