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.

Subscribe to Post Comments [Atom]

5 Comments:

At February 24, 2008 7:58 AM, Anonymous paul maurice martin said...

But stem cells themselves are vocal opponents of such research.

 
At February 24, 2008 11:09 AM, Blogger The Neurocritic said...

Thanks for sending the link to your poem. I wish the research had reached an advanced enough stage to help you now. I also wish you luck in your quest to educate "Christians" who value stem cells more than living, suffering human beings.

“...fuzzy stem-cell thinking –
The kind that makes us sick.”

 
At February 29, 2008 8:12 PM, Anonymous lazily anonymous said...

OK, I am lazy tonight. Did the authors have sham-operated rodents to compare the stem-implanted rodents with? Was there any electrophysiology done on the purported replacement neurons? What was the conversion rate of the NSCs to presumptive neurons? Did they do anything to stop the proliferation of the animal stem cells near the stroke damage? Is there any evidence that the transplanted cells, whatever their differentiation state, were not a source of (say) neurotrophic factors?

I admit these are annoying questions, but we should be getting to the point where these are the questions to ask. I can think of some interesting genetic manipulations you could try to tease apart the question of detecting activity in animal vs. human neurons in these animals (one idea: do the experiments in a line where you have messed with the locus of the early intermediate gene arc so that you will end up with arc mRNAs that differ in sequence between the hNSC derived neurons and animal ones and then use appropriately designed fluorescent probes...not that easy, but problably worth it).

 
At March 01, 2008 11:13 AM, Blogger The Neurocritic said...

I was pretty lazy too (i.e., I didn't read the paper, which is beyond my area of expertise). I spent a lot more time on the Family Guy image...

Here are the comments of Referee 1 (not that they ask the same questions as you, however).

 
At March 01, 2008 11:59 AM, Blogger The Neurocritic said...

OK, here are the answers to Lazily's questions, as far as I can tell.

(1) Sham-operated controls: YES

As a control group, we used rats subjected to ischemia and injected with the vehicle (n = 7).

This seems to have been only for the evaluation of sensorimotor function.

(2) Electrophysiology: NO [not really fair to ask the same investigators to do this].

(3a) Conversion rate in vitro:

Immunocytochemical analysis (Figure 2B–F) of 10 day-old cultures demonstrated that the proportion of nestin+ cells was 36.6±2.7%, 62.5±2.8% expressed the neuronal marker TuJ1, 1.9±0.3% expressed the astrocytic marker GFAP and 7.1±0.4% were oligodendrocytes and expressed galactocerebrocide (GC) (Figure 2F). A subset (9.8±1.6%) of the GFAP+ astrocytes co-expressed nestin [a neural-specific gene].

(3b) Survival and functional engraftment in vivo:

Grafted SD56 hNSCs, identified with hNuc, demonstrated a 37.0±15.8% survival rate and a remarkable dispersion toward the stroke-damaged tissue with no sign of overgrowth or tumorigenesis. The majority of grafted cells (61.2±4.7%) migrated at least 200 µm away from the injection site and penetrated an average distance of 806.4±49.3 µm into the stroke-damaged tissue.

(4) Anything to prevent proliferation of animal cells: ?? [don't think so].

(5) Transplanted cells a source of neurotrophic factors: don't know. They were cultured with EGF and FGF2, but don't know about transplanted cells themselves.

You can make a general comment on the paper if you'd like...

 

Post a Comment

Links to this post:

Create a Link

<< Home

eXTReMe Tracker