In the Stem Cellar: making better blood stem cells, a heart guard, iPS model points to ALS drug and tracking cells

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Major step in creating blood stem cells. If you track stem cells in any online news search, your feed perpetually will have numerous posts about attempts to find a bone marrow stem cell match for a desperate cancer patient. The power of those cells to reconstitute a person’s immune system after aggressive therapy saves the lives of thousands of cancer patients every year, but too many patients still die waiting to find an immunologically compatible donor.

Since pluripotent stem cells, both embryonic and iPS cells, can create any cell type in the body, they should be able to produce the needed blood forming stem cells. But that feat has been one of the toughest to accomplish in the young history of stem cell science. Blood stem cells created from pluripotent cells don’t self-renew like they should and don’t take up residence in the bone marrow properly. A CIRM-funded team at the University of California, Los Angeles, has made a major stride toward making this possible.

The team, led by Hanna Mikkola, started by looking at what genes were turned on in blood stem cells they created in the lab compared to natural ones. They pinpointed one set of genes, the HOXA genes, that is linked to the ability to self-renew. Next, they found that mimicking the effects of retinoic acid, a derivative of vitamin A, can turn on the HOXA genes.

 “Inducing retinoic acid activity at a very specific time in cell development makes our lab-created cells more similar to the real hematopoietic stem cells found in the body,” said Diana Dou, a graduate student in Mikkola’s lab in a UCLA press release.

While this is one major hurdle leaped, the team acknowledges they have more work to do before they can create lab-grown blood stem cell that fully match the functions of natural blood stem cells.

 

Turned-off gene protects hearts.  When Nobel Prize winner Shinya Yamanaka reprogrammed skin cells into embryonic-like iPS cells, he activated four genes that are very involved in embryo development, but have been assumed to be inactive in adults. Researchers at the University of Virginia published data overturning that dogma, and more importantly suggested that one of those genes, Oct4, is not just active in adults, it protects people from heart disease.

They found that Oct4 plays a role in the formation of atherosclerotic plaque. When that plaque buildup in arteries ruptures it causes heart attacks and strokes.  But Oct4 instructs smooth muscle cells to create protective fibrous caps that make the plaques less likely to rupture. The team leader, Gary Owen, speculated that Oct4 might also be involved in other aspects of the body’s effort to repair damage and heal wounds.

 “Finding a way to augment the expression of this gene in adult cells may have profound implications for promoting health and possibly reversing some of the detrimental effects with ageing,” said Owen in a story in Scicasts adapted from a university press release.

The researchers are now looking for ways to selectively activate Oct4 for therapeutic purposes.

 

neuronfromiPS

Nerves grown from iPS cells

Stem cell model leads to potential ALS drug.  In amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) motor nerves that allow all forms of movement die off. But, some nerves seem to be resistant to this damage. Researchers at Sweden’s Karolinska Institute and at the University of Milan in Italy have found that a specific nerve growth factor can protect motor nerves from ALS.

That factor, insulin-like growth factor 2 (IGF-2), was able to rescue human motor nerves grown in the lab from iPS-type stem cells made by reprogramming skin of ALS patients. The researchers then provided IGF-2 to mice with ALS-like disease through gene therapy and the animals lived longer than without the growth factor.

 “We can see that motor neurons are preserved and that IGF-2 treatment causes the axons to regenerate and recreate vital connections with muscles that were previously lost,” said Karolinska’s Eva Hedlund in a press release posted by MedicalXpress.

 Prior attempts to treat ALS patients with a related compound, IGF-1, by injecting it under the skin failed.  The current team suggests that direct delivery to motor nerves via gene therapy could provide a better outcome.

 

Labeling and tracking stem cells.  Numerous studies have shown stem cells grown in the lab function more like normal stem cells the closer the lab environment comes to mimicking the natural environment where the cells would grow in the body. Using that strategy a team at Carnegie Mellon University in Pittsburg succeeded in loading stem cells with an FDA-approved iron nanoparticle that will allow them to track the cells after transplant.

 

MSCs with iron nanoparticles

MSCs labeled with iron nanoparticles

They focused on a type of stem cell found in bone marrow, mesenchymal stem cells (MSCs), which are being used in more than half of the 600+ active stem cell clinical trials. To date, MSC trials have produced a very mixed bag of results, with much of the poorer outcomes attributed to the cells not going to, and staying, where they are needed.  So this tracking technique could help develop strategies to improve those outcomes.

Up to this point, researchers could not get the tracking agent into cells without using an agent to help get the particles across the cell membrane and those agents tend to disrupt the normal cell function. But, in their normal environment cells will engulf small particles on their own.  So the Carnegie team added other cells types found in bone marrow to their lab cultures, the MSCs felt more at home, and took up the nanoparticles. A neat little trick written up in a university press release posted at Science Daily.

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One thought on “In the Stem Cellar: making better blood stem cells, a heart guard, iPS model points to ALS drug and tracking cells

  1. “My little lost boy please share! His only chance is FDA approval of SMA rx It works https://twitter.com/ArtSlott/status/733716818993512449

    GSNPC-1 or Gwendolyn Strong Neuron Progenitor Cells.
    At the time of that first meeting in 2009, Dr. Keirstead’s research was the only potential treatment for SMA and he was quickly making his way through the FDA process. We toured his lab at UC Irvine, where he later kept Gwendolyn’s photo for all his researchers to remember why they were working so hard. We jumped on board and launched our second fundraising campaign “Unite for the Cure”, raising $150,000 in just four months with the help of 22 other SMA families and hundreds of individual donors. His SMA research was put on hold by the FDA, but Dr. Keirstead and Roman Reed continued to push and have since developed a groundbreaking cell-based technology.

    This technology is the basis for a cure for melanoma and has demonstrated utility in drug discovery, toxicity screening, and neurological research programs. In pilot testing, the cells have proven to effectively regenerate nerve growth sufficient to re-establish electrical impulses and motor function in animals with severed spinal cords. SCRP’s CSC 14 technology was also the basis of a very successful review for clinical use by England’s regulatory body for use in babies with spinal muscular atrophy. The launch of pre-clinical studies to further validate this GSNPC-1 technology is expected to begin at UC Irvine following completion of SCRP’s current capital raising efforts.

    The renaming of their exceptional patented technologies with broad and potentially “game changing” potential in restorative therapies is such a thoughtful gesture to help Gwendolyn’s NEVER GIVE UP. legacy live on. Thank you, Roman, Hans, and all those involved in making this happen. We are truly honored and hope millions benefit from GSNPC-1.
    http://thegsf.org/blog/detail/acts_of_kindness_research_named_for_gwendolyn/?

    What is going on? All these advances but no help to the suffering?

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