Stories that caught our eye: color me stem cells, delivering cell therapy with nanomagnets, and stem cell decisions

Nanomagnets: the future of targeted stem cell therapies? Your blood vessels are made up of tightly-packed endothelial cells. This barrier poses some big challenges for the delivery of drugs via the blood. While small molecules are able make their way through the small gaps in the blood vessel walls, larger drug molecules, including proteins and cells, are not able to penetrate the vessel to get therapies to diseased areas.

This week, researchers at Rice University report in Nature Communications on an ingenious technique using tiny magnets that may overcome this drug delivery problem.


At left, the nanoparticles are evenly distributed among the microtubules that help give the cells their shape. At right, after a magnetic field is applied, the nanoparticles are pulled toward one end of the cells and change their shapes. Credit: Laboratory of Biomolecular Engineering and Nanomedicine/Rice University

Initial studies showed that adding magnetic nanoparticles to the endothelial cells and then applying a magnetic field affected the cells’ internal scaffolding, called microtubules. These structures are responsible for maintaining the tight cell to cell connections. The team took the studies a step further by growing the cells in specialized petri dishes containing tiny, tube-shaped channels. Applying a magnetic field to the cells caused the cell-cell junctions to form gaps, making the blood vessel structures leaky. Simply turning off the magnetic field closed up the gaps within a few hours.

Though a lot of research remains, the team aims to apply this on-demand induction of cell leakiness along with adding the magnetic nanoparticles to stem cell therapy products to help target the treatment to specific area. In a press release, team leader Dr. Gang Bao spoke about possible applications to arthritis therapy:

“The problem is how to accumulate therapeutic stem cells around the knee and keep them there. After injecting the nanoparticle-infused cells, we want to put an array of magnets around the knee to attract them.”

To differentiate or not differentiate: new insights During the body’s development, stem cells must differentiate, or specialize, into functional cells – like liver, heart, brain. But once that specialization occurs, the cells lose their pluripotency, or the ability to become any type of cell. So, stem cells must balance the need to differentiate with the need to make copies of itself to maintain an adequate supply of stem cells to complete the development process. And even after a fully formed baby is born, it’s still critical for adult stem cells to balance the need to regenerate damaged tissue versus stashing away a pool of stem cells in various organs for future regeneration and replacement of damaged or diseased tissues.


Visualizing activation of Nanog gene activity (bright green spot) within cell nucleus. 
Image: Courtesy of Bony De Kumar, Ph.D., and Robb Krumlauf, Ph.D., Stowers Institute for Medical Research

A report this week in the Proceedings of the National Academy of Sciences finds evidence that the two separate processes – differentiation and pluripotency – directly communicate with each other as way to ensure a proper balance between the two states.

The study, carried out by researchers at Stowers Institute for Medical Research in Kansas City, Missouri, focused on the regulation of two genes: Nanog and Hox. Nanog is critical for maintaining a stem cell’s ability to become a specialized cell type. In fact, it’s one of the four genes initially used to reprogram adult cells back into induced pluripotent stem cells. The Hox gene family is responsible for generating a blueprint of the body plan in a developing embryo. Basically, the pattern of Hox gene activity helps generate the body plan, basically predetermining where the various body parts and organs will form.

Now, both Nanog and Hox proteins act by binding to DNA and turning on a cascade of other genes that ultimately maintain pluripotency or promote differentiation. By examining these other genes, the researchers were surprised to find that both Nanog and Hox were bound to both the pluripotency and differentiation genes. They also found that Nanog and Hox can directly inhibit each other. Taken together, these results suggest that exquisite control of both processes occurs cross regulation of gene activity.

Dr. Robb Krumlauf one of authors on the paper talked about the significance of the result in a press release:

“Over the past 10 to 20 years, biologists have shown that cells are actively assessing their environment, and that they have many fates they can choose. The regulatory loops we’ve found show how the dynamic nature of cells is being maintained.”

Color me stem cells Looking to improve your life and the life of those around you? Then we highly recommend you pay a visit to today’s issue of Right Turn, a regular Friday feature of  Signals, the official blog of CCRM, Canada’s public-private consortium supporting the development of regenerative medicine technologies.


Collage sample of CCRM’s new coloring sheets. Image: copyright CCRM 2017

As part of an public outreach effort they have created four new coloring sheets that depict stem cells among other sciency topics. They’ve set up a DropBox link to download the pictures so you can get started right away.

Adult coloring has swept the nation as the hippest new pastime. And it’s not just a frivolous activity, as coloring has been shown to have many healthy benefits like reducing stressed and increasing creativity. Just watch any kid who colors. In fact, share these sheet with them, it’s intended for children too.

Earliest stem cells made in lab; provide “extraordinary” potential

Embryonic stem cells are classified as pluripotent cells because they are able (“potent”) to mature into almost every (“pluri”) cell type. Thanks to Nobel Prize winner Shinya Yamanaka, researchers have been able to reprogram fully matured cells, like skin or blood, into embryonic stem cell-like induced pluripotent stem cells (iPS). The technique has revolutionized stem cell science, providing human models of disease and the prospect of personalized cell therapies.


Human embryo about to complete 1st cell division. Each of these cells are totipotent: they have the ability (“potent”) can give rise to all (“toti”) the cell types of the developing embryo including placenta and umbilical cord. (Image credit: The Endowment for Human Development)

And yet it has remained unknown if reprogramming cells resembling so-called totipotent cells is possible. Unlike iPS or embryonic stem cells, totipotent cells have complete shape-shifting abilities in that they can give rise to all (“toti”) the cell types of the developing embryo including the placenta and umbilical cord. They appear briefly during the earliest stages of development when the fertilized embryo is made up of just one or a few cells. Could lab-derived totipotent cells provide an equally or even more powerful research tool than iPS cells?

The stem cell field is now in position to ask that question. This week scientists from French Institute of Health and Medical Research (INSERM) and the Max Planck Institute in Germany report in Nature Structural Biology that they successfully induced mouse embryonic stem cells to take on totipotent characteristics.


That question mark over the blue arrow can be removed after this week’s report that pluripotent stem cells can be induced to take on characteristics of totipotent cells. (image credit: IGBMC)

To achieve this feat, the scientists started with the known observation that a small amount of totipotent cells spontaneously appear when growing pluripotent stem cells in petri dishes. They are called 2C-like cells because of their likeness to the cells of the two-cell embryo. The team isolated those 2C cells and carefully compared them to the pluripotent embryonic stem cells. They noticed the DNA in 2C cells had a looser structure, which indicates more flexibility to switch on many different genes in a cell. With this information, they found that a protein called CAF1 known to play a role in making a tighter DNA structure, and inhibiting genes, was reduced in the totipotent 2C cells.

By experimentally blocking the function of CAF1 in pluripotent cells, the tightened DNA structure was loosened, leading to more genes being switched on and inducing a totipotent state. With these cells in hand, the team can now examine their possible impact on accelerating progress in regenerative medicine. Maria-Elena Torres-Padilla, the lead scientist on the project, pointed out in a press release the significance of these cells for future studies:

“Totipotency is a much more flexible state than the pluripotent state and its potential applications are extraordinary.”