Tuesday, January 09, 2007

"Pluripotent" Amniotic/Placental Stem Cells

I've just skimmed the Nature Biotechnology article (free abstract and references with free registration to Nature.com, the article is for subscription or by individual purchase, only)by Atala, De Coppi, et. al, "Isolation of amniotic stem cell lines with potential for therapy" (Nature Biotechnology - 25, 100 - 106 (2007). Published online: 7 January 2007; | doi:10.1038/nbt1274)

The authors claim that the cells are pluripotent.
This is not being publicized as much as I would like it to be. Please, when you call your Representative and Senators about the vote that is planned for Thursday, on HR 3, please let them know that these cells may, indeed, be more useful and are much more ethically acceptible than embryonic stem cells from "spare" embryos.

The cells can be obtained from placenta as well as amniotic fluid, so can be harvested without risk to the baby.

The cell lines were evaluated through 120 doublings and appear to be stable. All cell lines were confirmed in mice, using human stem cells implanted into mice that are immune-deficient. There were no teratomas. The human cells repaired damage in the mouse brains, in mice with a disease similar to Krabbe's disease. While the production of dopamine is not documented, the cells also developed along the lines of dopaminergic cells - the cells that are diseased in Parkinson's.

While the use of human nerve cells in the mouse brain could be considered ethically problematic, this is a very significant finding.

The researchers report that they were able to produce several lines of cells, and to prove that some of these cell lines are functional.

"We conclude that the AFS cells are indeed broad-spectrum multipotent (that is, pluripotent) stem cells."


Potential sources of AFS cells in the developing fetus are diverse31.
CD117 (c-Kit), the surface marker used for immunoselection of AFS
cells, plays an important role in gametogenesis, melanogenesis and
hematopoiesis32,33. This receptor protein is present on human ES
cells34, primordial germ cells and many somatic stem cells, including,
but not limited to, those of the neural crest35,36. Despite sharing
expression of c-Kit, AFS cells appear clearly distinct from ES cells, germline stem cells and certain adult stem cell populations, such as hematopoietic stem cells, on the basis of differences both in a variety of cell surface markers and in gene expression patterns assessed by transcriptional profiling37. Thus, the role of AFS cells in ontogeny is not yet clear.
AFS cells can serve as precursors to a broad spectrum of differentiated cell types. We used retroviral marking of AFS cell clones to rigorously assess their multipotent character. Cells from a marked clone were induced to differentiate along six distinct lineages (adipogenic, osteogenic, myogenic, endothelial, neurogenic and hepatic). DNA of the resulting specialized cells contained a unique marker junction fragment between proviral and cellular sequences in the genome. In addition to the markers and cell types documented here, we have demonstrated that human AFS cells of the same clone can be induced to express markers characteristic of cardiac muscle, including cardiac myosin, troponin I and troponin T, and of pancreatic beta-cells, including Pax6, neurogenin D and insulin (data not shown). Human AFS cells can therefore yield differentiated cells corresponding to each of the three embryonic germ layers. The full range of adult somatic cells to which AFS cells can give rise remains to be determined.


. . .
AFS cells are able to differentiate along adipogenic, osteogenic,
myogenic, endothelial, neurogenic and hepatic pathways.We show the
acquisition of lineage-specific functionality by AFS cells differentiated
in vitro toward neurons, osteoblasts and hepatocytes. For some cell
types, acquisition of a full terminally differentiated phenotype is
difficult to achieve in culture. The expression of characteristic functions
may demand multistage protocols, as exemplified here by the
expression of GIRK channels after neurogenic differentiation. Similarly,
we observed urea secretion after hepatogenic differentiation. This
represents a liver-specific function that requires the coordinated
expression of several enzymes and specific mitochondrial amino
acid transporters.


Note - edited for the spelling of De Coppi, and for a correction concerning "Krabbe's Disease." (The disease treated with fetal stem cells was "Batten's Disease."

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