Biomedical Engineering Reference
In-Depth Information
absence of transcriptional regulator Ptf1a the pancreatic progenitors change their
fate and develop into the intestinal epithelium [
139
]. Therefore, it can be suggested
that adult stem/progenitor cells from these tissues might be easier to differentiate
toward a pancreatic lineage.
Apart from hepatic oval cells discussed above, there are some other stem/
progenitor-like cells in the liver that have the potential to generate insulin-pro-
ducing cells. Yamada et al. [
140
] demonstrated the conversion of hepatic stem-like
cells (HSLs) into pancreatic endocrine cells following treatment with sodium
butyrate and betacellulin. In another study, Nakajima et al. [
141
] showed that
small hepatocytes (SHCs), a type of adult hepatic progenitor cells, could differ-
entiate into cells producing insulin. The gastrointestinal tract contains a large
population of stem cells that can be utilized for therapeutic approaches. However,
their potential for the generation of b cells is largely unexplored. GLP-1
(1-37)
treatment was shown to induce insulin production in fetal and adult intestinal
epithelial cells both in vitro and in vivo. Such in vitro-generated cells were able to
reverse hyperglycemia following transplantation into diabetic mice [
142
].
Stem Cells from Adult Bone Marrow
Adult bone marrow contains a population of multipotent progenitor stem cells that
have the potential to differentiate into hematopoietic cells as well as into cells of
some non-hematopoietic tissues [
143
]. As discussed in the previous section,
hematopoietic stem cells from bone marrow have a beneficial immunomodulatory
effect in the treatment of type 1 diabetes. However, whether they directly trans-
differentiate to generate b cells is still controversial. Lanus et al. [
143
] detected
donor bone marrow-derived b cells in recipient pancreas within 4-6 weeks of
transplantation. They used a Cre/loxP system with EGFP (enhanced GFP) reporter
to confirm the origin of newly generated b cells. Furthermore, they confirmed that
these new b cells were resulting from transdifferentiation of donor bone marrow
cells and not by any cell fusion. In another study Hess et al. [
144
] showed that the
transplantation of adult bone marrow-derived stem cells into streptozotocin-
induced diabetic mice resulted in the reduction of hyperglycemia. In this case,
donor cells promoted endogenous pancreas regeneration and only a few of them
converted into b cells. In contrast, some other studies did not find any significant
evidence of bone marrow transdifferentiation into b cells following transplantation
[
145
,
146
]. Using a different strategy, Oh et al. [
147
] showed the in vitro
transdifferentiation of bone marrow-derived cells into insulin-producing cells
when cultured under specific conditions. From these studies the in vivo generation
of b cells from transplanted bone marrow-derived cells seems to be infrequent.
However, bone marrow-derived cells can still be a potential source of adult stem
cells for the in vitro generation of b cells.
