Stem Cell Roundup: Lab-grown meat, stem cell vaccines for cancer and a free kidney atlas for all

Here are the stem cell stories that caught our eye this week.

Cool Stem Cell Photo: Kidneys in the spotlight

At an early stage, a nephron forming in the human kidney generates an S-shaped structure. Green cells will generate the kidneys’ filtering device, and blue and red cells are responsible for distinct nephron activities. (Image/Stacy Moroz and Tracy Tran, Andrew McMahon Lab, USC Stem Cell)

I had to take a second look at this picture when I first saw it. I honestly thought it was someone’s scientific interpretation of Vincent van Gogh’s Starry Night. What this picture actually represents is a nephron. Your kidney has over a million nephrons packed inside it. These tiny structures filter our blood and remove waste products by producing urine.

Scientists at USC Stem Cell are studying kidney development in animals and humans in hopes of gaining new insights that could lead to improved stem cell-based technologies that more accurately model human kidneys (by coincidence, we blogged about another human kidney study on Tuesday). Yesterday, these scientists published a series of articles in the Journal of American Society of Nephrology that outlines a new, open-source kidney atlas they created. The atlas contains a catalog of high resolution images of different structures representing the developing human kidney.

CIRM-funded researcher Andrew McMahon summed it up nicely in a USC news release:

“Our research bridges a critical gap between animal models and human applications. The data we collected and analyzed creates a knowledge-base that will accelerate stem cell-based technologies to produce mini-kidneys that accurately represent human kidneys for biomedical screening and replacement therapies.”

And here’s a cool video of a developing kidney kindly provided by the authors of this study.

Video Caption: Kidney development begins with a population of “progenitor cells” (green), which are similar to stem cells. Some progenitor cells (red) stream out and aggregate into a ball, the renal vesicle (gold). As each renal vesicle grows, it radically morphs into a series of shapes — can you spot the two S-shaped bodies (green-orange-pink structures)? – and finally forms a nephron. Each human kidney contains one million mature nephrons, which form an expansive tubular network (white) that filters the blood, ensuring a constant environment for all of our body’s functions. (Video courtesy of Nils Lindstorm, Andy McMahon, Seth Ruffins and the Microscopy Core Facility at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the Keck School of Medicine of USC)


Lab-grown hamburgers coming to a McDonald’s near you…

“Lab-grown meat is coming, whether you like it or not” sure makes a splashy headline! This week, Wired magazine featured two Bay Area startup companies, Just For All and Finless Foods, dedicated to making meat-in-a-dish in hopes of one day reducing our dependence on livestock. The methods behind their products aren’t exactly known. Just For All is engineering “clean meat” from cells. On the menu currently are cultured chorizo, nuggets, and foie gras. I bet you already guessed what Finless Foods specialty is. The company is isolating stem-like muscle progenitor cells from fish meat in hopes of identifying a cell that will robustly create the cell types found in fish meat.

Just’s tacos made with lab-grown chorizo. (Wired)

I find the Wired article particularly interesting because of the questions and issues Wired author Matt Simon raises. Are clean meat companies really more environmentally sustainable than raising livestock? Currently, there isn’t enough data to prove this is the case, he argues. And what about the feasibility of convincing populations that depend on raising livestock for a living to go “clean”? And what about flavor and texture? Will people be willing to eat a hamburger that doesn’t taste and ooze in just the right way?

As clean meat technologies continue to advance and become more affordable, I’ll be interested to see what impact they will have on our eating habits in the future.


Induced pluripotent stem cells could be the next cancer vaccine

Our last story is about a new Cell Stem Cell study that suggests induced pluripotent stem cells (iPSCs) could be developed into a vaccine against cancer. CIRM-funded scientist Joseph Wu and his team at Stanford University School of Medicine found that injecting iPSCs into mice that were transplanted with breast cancer cells reduced the formation of tumors.

The team dug deeper and discovered that iPSCs shared similarities with cancer cells with respect to the panel of genes they express and the types of proteins they carry on their cell surface. This wasn’t surprising to them as both cells represent an immature development stage. Because of these similarities, injecting iPSCs primed the mouse’s immune system to recognize and reject similar cells like cancer cells.

The team will next test their approach on human cancer cells in the lab. Joseph Wu commented on the potential future of iPSC-based vaccines for cancer in a Stanford news release:

“Although much research remains to be done, the concept itself is pretty simple. We would take your blood, make iPS cells and then inject the cells to prevent future cancers. I’m very excited about the future possibilities.”

 

Have your cake and eat it too: Stem cells without the risk of tumors

journal.pmed.1000029.g001

An unregulated stem cell treatment in 2001 led to tumor growth in the (A) brain stem and (B) spinal cord of the patient four years later. (Fig 1. PLoS Med. 2009 Feb 17;6(2):e1000029)

A real stem cell tourism story
Back in 2001, an Israeli boy suffering from Ataxia Telangiectasia, a genetic brain disease that affects movement, traveled to Russia for an unregulated stem cell treatment. His brain and spinal cord were injected with fetal stem cells though the exact composition of those cells was not known. Four years later, the boy complained of headaches and his doctors back home found tumors in his brain and spinal cord.

 Stem cells: a double-edged sword
As the BBC  and many other news outlets reported in 2009, a Plos Medicine report eventually confirmed the tumor cells originated from the donor stem cells. And here lies a double-edged sword of stem cell-based therapies. On one side, stem cells hold great promise to repair diseased or damaged tissue because they can morph, or differentiate, into a wide range of cell types.

 But on the other side, they have the capacity to remain unspecialized and continually self-renew.This is great for producing enough cells to treat many people. Researchers try to make sure only more mature cells are transplanted, but if any of these propagating, undifferentiated cells get carried along with a stem cell-based treatment, there’s a risk of introducing uncontrolled cell growth and cancers instead of remedies. Human pluripotent stem cells (hPSCs), which can form almost any cell type found in our body, are believed to be especially susceptible to this dangerous potential side effect.

Reporting this week in the journal, eLife, CIRM-funded researchers at UCSD found a way to dodge the risk of tumor growth by identifying a unique, alternate stem cell type that could be applied to kidney disease. To find this cell type, the research team focused on cells that were a bit further along a differentiation path compared to unspecialized hPSCs.

Repeat after me: endoderm, ectoderm, mesoderm

In the earliest stages of embryo development, three germ layers form. (image: Internet Science Room)

In the earliest stages of embryo development, three germ layers form. (image: Internet Science Room)

To explain, let’s take a brief detour into developmental biology. In the very early stages of specialization, the cells of the embryo form the three germ layers: ectoderm, endoderm and mesoderm. Each layer gives rise to specific set of cells and tissues. Endoderm forms, to just name a few, the lungs, intestines and pancreas; ectoderm develops into skin, the brain and spinal cord; mesoderm forms blood, muscle, bone and kidneys. Within each germ layer lie progenitor stem cells, that maintain the capacity to self-renew and can also differentiate into the adult cells formed by that germ layer.

Finding a mesoderm progenitor
While methods for growing ectoderm and endoderm progenitor stem cells from hPSCs had been previously developed, few, if any, labs had done the same for mesoderm. So the UCSD team systematically tested thousands of combinations of nutrients and chemicals for both growing and differentiating hPSCs into mesoderm. Using this approach, they successfully tracked down a recipe that gave rise to mesoderm progenitor cells with the potential to multiply and grow in population yet lacking the ability to form tumors when transplanted into mice.

Color tagged surface proteins indicate a kidney fate for activated mesodermal progenitors (Fig 7c Kumar et al. eLife 2015;4:e08413)

Color tagged surface proteins indicate a kidney fate for activated mesodermal progenitors (Fig 7c Kumar et al. eLife 2015;4:e08413)

The research team planned to work out the various conditions to specialize the progenitor cells into a wide range of mesoderm tissues. But to their surprise, when triggered to differentiate, the progenitors only gave rise to cells of the kidney. This very limited specialization is actually desired for clinical applications since purity of cell therapies is a requirement for testing in humans.

Our kidneys thank you
Putting it all together, the team has identified a cell source with unlimited self renewal capacity that can differentiate into a very specific cell type and doesn’t carry a risk of tumor formation when transplanted. These qualities make the mesoderm progenitor cell an exciting tool for developing future kidney repair or replacement treatments. And as Dr. Karl Willert, senior author and associate professor at UC San Diego, states in a UCSD press release, there is also reason to be excited about near-term applications:

“Our cells can serve as building blocks to generate kidneys that may one day be suitable for cell replacement and transplantation. I think such a therapeutic application is still a few years in the future, but engineered kidney tissue can serve as a powerful model system to study how the human kidney interacts with and filters drugs. Such an application would be of tremendous value to the pharmaceutical industry.”