Biomedical Engineering Reference
In-Depth Information
conclusive evidence is missing because of the lack of a specific pancreatic stem
cell marker.
Pancreatic duct cells
Pancreatic endocrine cells are generated from ductal progenitors during
embryonic development and it has also been shown that ductal cells can give rise
to b cells under certain conditions even in the adult pancreas [
27
]. Therefore
pancreatic ductal population presents as a probable source for the existence of
stem cells. Indeed, Ramiya et al. [
123
] reported the generation of islet-like clus-
ters, containing a, b, and d cells, from the long-term culture of pancreatic ductal
cells from the adult pre-diabetic NOD mice. These in vitro-generated islets were
glucose responsive and were able to reverse diabetes when transplanted into
diabetic NOD mice. In another study, Bonner-Weir et al. [
124
] showed the
generation of insulin-positive cells from human adult pancreatic ductal cells grown
in a monolayer and overlaid with a thin layer of matrigel. More recently,
Yamamoto et al. [
125
] and Noguchi et al. [
126
] also showed the isolation of
pancreatic stem/progenitor cells from mouse ductal rich population that were able
to generate hormone producing cells under specific conditions. These putative
stem cells were able to divide actively beyond the population doubling level of
300. However, a similar approach was not successful with cells from human ductal
rich population [
127
]. Although, these studies provide evidence in favor of the
existence of stem cells in ductal population, there still remains an element of
doubt. It is also possible that ductal cells just dedifferentiate to lose their ductal
phenotype before converting into endocrine cells. This problem exists due to the
absence of known markers to specify pancreatic stem cells.
Nestin-positive cells
Nestin-positive cells are considered as another candidate for adult pancreatic
stem cells. Nestin is an intermediate filament protein that has been shown as a
marker for neural stem cells [
128
]. In a study by Zulewski et al. [
129
], nestin-
positive cells were isolated from rat and human islets. These cells showed
extended proliferative capacity during in vitro culture (nearly 8 months) and were
able to differentiate into pancreatic endocrine, exocrine, and hepatic phenotypes.
Such nestin-positive cells did not express any of the islet hormones or cytokeratin
19 (CK-19), a marker of the ductal cells, indicating that they exist as a separate
population in the pancreas. However, nestin-positive cells are found in many other
tissues as well, making nestin a poor marker for the identification of pancreatic
stem cells [
130
]. Therefore, in spite of their potential to contribute toward islet
differentiation, their role as the true pancreatic stem cells remains elusive.
Small cells and oval cells
Using in vitro culture of human and canine islets, Petropavlovskaia and
Rosenberg [
131
] identified a cluster of small cells that were positive for pancreatic
endocrine hormones but were negative for nestin, CK-19, or amylase (a marker of
acinar cells). Such small cells had an immature morphology and secreted insulin in
response to glucose stimulation. However, these cells were extremely quiescent
and difficult to expand in culture. Therefore, even if they contribute toward islet
growth, they are not a useful source for the in vitro generation of b cells. Another
