Liver Directed Cell Therapy for Type 1 Diabetes Mellitus

Diabetes Freedom

Treatments for Diabetes

Get Instant Access

It is reasonable to conclude that liver-directed cell therapy has prospects for type 1 diabetes mellitus. Besides the developmental relationships between liver and pancreas, additional evidence indicates that hepatocyte-like cells can emerge in the pancreas. Such evidence includes studies in hamsters or rats treated with carcinogens or peroxisome proliferators (96,97), dietary copper depletion and repletion in rats (20,98), transgenic mice expressing keratinocyte growth factor under insulin promoter (99), and transplantation of murine pancreatic oval cells in FAH mice (21). On the other hand, some liver tumors display typical pancreatic markers (e.g., amylase and lipase) (100). Pancreatic genes are expressed in sorted fetal mouse liver cells, including the P-cell transcription factor, Pdx-1, as well as amylase and lipase (27). Moreover, expression of transgenes, such as Pdx-1 or neuroD-P cellulin in liver cells induces insulin expression in rodent and human cells (101-104). This particular finding should be of much interest because certain progenitor cell populations in the fetal or adult liver, including those with oval cell properties, are thought to be amenable to such genetic manipulation. Because insulin expression in pancreatic P cells is driven in a hierarchical manner, including HNF-3p-mediated transcriptional regulation of Pdx-1 gene expression followed by additional contributions from neuroD and several other transcription factors, it stands to reason that the transcriptional machinery in some cells will be amenable to genetic modulation. If these manipulations could be combined with effective cell populations that could be transplanted, one would begin to advance cell therapy for diabetes mellitus. For instance, reconstitution of telomerase activity in fetal human liver stem/progenitor cells was associated with extensive replication and immortalization of cells without evidence for oncogenic perturbations (17). These cells expressed a variety of transcription factors observed in liver cells. Moreover, in response to Pdx-1 transgene expression, cells began to express insulin in a regulated fashion, although all elements of p-cell phenotype were not reproduced (103). Nonetheless, transplantation of Pdx-1-expressing immortalized fetal human liver cells in diabetic immunotolerant mice resulted in correction of hyperglycemia.

Was this article helpful?

0 0
Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

Get My Free Ebook

Post a comment