Sunday, February 24, 2008

Stem Cells for Peter's McStroke


Fig 3 (Daadi et al., 2008). Dispersion, engraftment and differentiation of the hNSCs [human neural stem cells] in stroke-lesioned animals.
Stem cells helped repair stroke damage in rats, early Stanford study shows

By AMY ADAMS

STANFORD, Calif.
— Neural cells derived from human embryonic stem cells helped repair stroke-related damage in the brains of rats and led to improvements in their physical abilities after a stroke, according to a new study by researchers at the Stanford University School of Medicine.

This study, published in the Feb. 20 issue of the journal Public Library of Science-ONE, marks the first time researchers have used human embryonic stem cells to generate neural cells that grow well in the lab, improve a rat’s physical abilities and consistently don’t form tumors when transplanted.

Though the authors caution that the study is small and that more work is needed to determine whether a similar approach would work in humans, they said they believe it shows the potential for using stem cell therapies in treating strokes.
In the Family Guy episode entitled McStroke, Peter Griffin rescues a man from a burning building -- the fast food restaurant McBurgertown. It turns out the man is the the owner of McBurgertown, who then
offers Peter a lifetime supply of burgers as thanks for his heroism. Peter accepts this offer... However, after eating 30 burgers in one sitting, he suffers a severe stroke and is hospitalized. The entire left side of his body is paralyzed, forcing him to limp around on one leg, with his arm hanging lifelessly on his side and part of his face severely hanging over.1 This lifestyle proves to be difficult for Peter for the next three months, and he blames McBurgertown for his problems. Wondering if there is anything that can be done to return to his regular regime, he decides to give stem cell research a try and, after a mere 5 minutes, Peter returns completely fine.
"Why are we not funding this?!" he asks after walking out of the stem cell research facility, completely restored.


Footnote

1 Although politically incorrect (as usual), the cartoon does a reasonable job at trying to portray hemiplegia, paralysis of one half of the body (although the Picasso-esque rendition of his facial droop is a bit much).

Reference

Daadi MM, Maag AL, Steinberg GK. (2008). Adherent self-renewable human embryonic stem cell-derived neural stem cell line: functional engraftment in experimental stroke model. PLoS ONE Feb 20; 3(2):e1644.

BACKGROUND: Human embryonic stem cells (hESCs) offer a virtually unlimited source of neural cells for structural repair in neurological disorders, such as stroke. Neural cells can be derived from hESCs either by direct enrichment, or by isolating specific growth factor-responsive and expandable populations of human neural stem cells (hNSCs). Studies have indicated that the direct enrichment method generates a heterogeneous population of cells that may contain residual undifferentiated stem cells that could lead to tumor formation in vivo. METHODS/PRINCIPAL FINDINGS: We isolated an expandable and homogenous population of hNSCs (named SD56) from hESCs using a defined media supplemented with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and leukemia inhibitory growth factor (LIF). These hNSCs grew as an adherent monolayer culture. They were fully neuralized and uniformly expressed molecular features of NSCs, including nestin, vimentin and radial glial markers. These hNSCs did not express the pluripotency markers Oct4 or Nanog, nor did they express markers for the mesoderm or endoderm lineages. The self-renewal property of the hNSCs was characterized by a predominant symmetrical mode of cell division. The SD56 hNSCs differentiated into neurons, astrocytes and oligodendrocytes throughout multiple passages in vitro, as well as after transplantation. Together, these criteria confirm the definitive NSC identity of the SD56 cell line. Importantly, they exhibited no chromosome abnormalities and did not form tumors after implantation into rat ischemic brains and into naïve nude rat brains and flanks. Furthermore, hNSCs isolated under these conditions migrated toward the ischemia-injured adult brain parenchyma and improved the independent use of the stroke-impaired forelimb two months post-transplantation. CONCLUSIONS/SIGNIFICANCE: The SD56 human neural stem cells derived under the reported conditions are stable, do not form tumors in vivo and enable functional recovery after stroke. These properties indicate that this hNSC line may offer a renewable, homogenous source of neural cells that will be valuable for basic and translational research.

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