stem cells
Tackling Cancer Metastasis with Engineered Blood Platelets
Posted on by Dr. Francis Collins
Credit: Dan Hixson/University of Utah College of Engineering, Salt Lake City
When cancer cells spread to new parts of the body in a process called metastasis, they often get there by traveling through the bloodstream. To avoid alerting the immune system and possibly triggering their demise, cancer cells coax circulating blood platelets to glom onto their surfaces and mask them from detection. This deceptive arrangement has raised a tantalizing possibility: What if blood platelets could be programmed to recognize and take out those metastasizing cancer cells?
Tara Deans, University of Utah, Salt Lake City, was recently awarded a 2019 NIH Director’s New Innovator Award to do exactly that. It’s an exciting opportunity for a researcher who stumbled onto this innovative strategy quite by accident.
Deans is a bioengineer and expert in designing synthetic gene circuits. These circuits consist of small collections of genetic “parts” that can be assembled and integrated to program cells to behave differently than their natural counterparts [1]. In her initial work, Deans got these specialized gene circuits to prompt blood-forming stem cells to mass-produce platelets in the lab.
But blood platelets are unusual cells. They’re packed with many proteins that help to repair small nicks in blood vessels and stop the bleeding when we’re injured. Blood platelets do so even though they lack a nucleus and DNA to encode and make any of the proteins. Their protein cargo is pre-packaged and comes strictly from the bone marrow cells, called megakaryocytes, that produce them.
Deans realized that engineering platelets might pose a rare opportunity. She could wire the needed circuitry into the blood-forming stem cells and engineer them to make any desired therapeutic proteins, which are then loaded into the blood platelets for their 8- to 10-day lifespan. She started out producing blood platelets that could safely carry functional replacement enzymes in people with certain rare metabolic disorders.
As this research progressed, Deans got some troubling personal news: A friend was diagnosed with a blood cancer. At the time, Deans didn’t know much about the diagnosis. But, in reading about her friend’s cancer, she learned how metastasizing tumor cells interact with platelets.
That’s when Deans had her “aha” moment: maybe the engineered platelets could also be put to work in preventing metastasizing tumor cells from spreading.
Now, with her New Innovator Award, Deans will pursue this novel approach by engineering platelets to carry potentially promising cancer-fighting proteins. In principle, they could be tailored to fight breast, lung, and various other cancer types. Ultimately, she hopes that platelets could be engineered to target and kill circulating cancer cells before they move into other tissues.
There’s plenty of research ahead to work out the details of targeting the circulating cancer cells and then testing them in animal models before this strategy could ever be attempted in people. But Deans is excited about the path forward, and thinks that platelets hold great promise to function as unique drug delivery devices. It has not escaped her notice that this approach could work not only for controlling the spread of cancer cells, but also in treating other medical conditions.
Reference:
[1] Genetic circuits to engineer tissues with alternative functions. Healy CP, Deans TL. J Biol Eng. 2019 May 3;13:39.
Links:
Metastatic Cancer (National Cancer Institute/NIH)
Deans Lab (University of Utah, Salt Lake City)
Deans Project Information (NIH RePORTER)
NIH Director’s New Innovator Award (Common Fund)
NIH Support: Common Fund; National Cancer Institute
Watch Flowers Spring to Life
Posted on by Dr. Francis Collins
Spring has sprung! The famous Washington cherry blossoms have come and gone, and the tulips and azaleas are in full bloom. In this mesmerizing video, you’ll get a glimpse of the early steps in how some spring flowers bloom.
Floating into view are baby flowers, their cells outlined (red), at the tip of the stem of the mustard plant Arabidopsis thaliana. Stem cells that contain the gene STM (green) huddle in the center of this fast-growing region of the plant stem—these stem cells will later make all of the flower parts.
As the video pans out, slightly older flowers come into view. These contain organs called sepals (red, bumpy outer regions) that will grow into leafy support structures for the flower’s petals.
Movie credits go to Nathanaёl Prunet, an assistant professor at the University of California, Los Angeles, who shot this video while working in the NIH-supported lab of Elliot Meyerowitz at the California Institute of Technology, Pasadena. Prunet used confocal microscopy to display the different ages and stages of the developing flowers, generating a 3D data set of images. He then used software to produce a bird’s-eye view of those images and turned it into a cool movie. The video was one of the winners in the Federation of American Societies for Experimental Biology’s 2018 BioArt competition.
Beyond being cool, this video shows how a single gene, STM, plays a starring role in plant development. This gene acts like a molecular fountain of youth, keeping cells ever-young until it’s time to grow up and commit to making flowers and other plant parts.
Like humans, most plants begin life as a fertilized cell that divides over and over—first into a multi-cell embryo and then into mature parts, or organs. Because of its ease of use and low cost, Arabidopsis is a favorite model for scientists to learn the basic principles driving tissue growth and regrowth for humans as well as the beautiful plants outside your window. Happy Spring!
Links:
Meyerowitz Lab (California Institute of Technology, Pasadena)
Prunet Lab (University of California, Los Angeles)
The Arabidosis Information Resource (Phoenix Bioinformatics, Fremont, CA)
BioArt Scientific Image and Video Competition (Federation of American Societies for Experimental Biology, Bethesda, MD)
NIH Support: National Institute of General Medical Sciences
Studying Color Vision in a Dish
Posted on by Dr. Francis Collins
Credit: Eldred et al., Science
Researchers can now grow miniature versions of the human retina—the light-sensitive tissue at the back of the eye—right in a lab dish. While most “retina-in-a-dish” research is focused on finding cures for potentially blinding diseases, these organoids are also providing new insights into color vision.
Our ability to view the world in all of its rich and varied colors starts with the retina’s light-absorbing cone cells. In this image of a retinal organoid, you see cone cells (blue and green). Those labelled with blue produce a visual pigment that allows us to see the color blue, while those labelled green make visual pigments that let us see green or red. The cells that are labeled with red show the highly sensitive rod cells, which aren’t involved in color vision, but are very important for detecting motion and seeing at night.
Modeling Hypertrophic Cardiomyopathy in a Dish
Posted on by Dr. Francis Collins
Credit: Zhen Ma, University of California, Berkeley
Researchers have learned in recent years how to grow miniature human hearts in a dish. These “organoids” beat like the real thing and have allowed researchers to model many key aspects of how the heart works. What’s been really tough to model in a dish is how stresses on hearts that are genetically abnormal, such as in inherited familial cardiomyopathies, put people at greater risk for cardiac problems.
Enter the lab-grown human cardiac tissue pictured above. This healthy tissue comprised of the heart’s muscle cells, or cardiomyocytes (green, nuclei in red), was derived from induced pluripotent stem (iPS) cells. These cells are derived from adult skin or blood cells that are genetically reprogrammed to have the potential to develop into many different types of cells, including cardiomyocytes.
Study Shows Genes Unique to Humans Tied to Bigger Brains
Posted on by Dr. Francis Collins
Caption: Cortical organoid, showing radial glial stem cells (green) and cortical neurons (red).
Credit: Sofie Salama, University of California, Santa Cruz
In seeking the biological answer to the question of what it means to be human, the brain’s cerebral cortex is a good place to start. This densely folded, outer layer of grey matter, which is vastly larger in Homo sapiens than in other primates, plays an essential role in human consciousness, language, and reasoning.
Now, an NIH-funded team has pinpointed a key set of genes—found only in humans—that may help explain why our species possesses such a large cerebral cortex. Experimental evidence shows these genes prolong the development of stem cells that generate neurons in the cerebral cortex, which in turn enables the human brain to produce more mature cortical neurons and, thus, build a bigger cerebral cortex than our fellow primates.
That sounds like a great advantage for humans! But there’s a downside. Researchers found the same genomic changes that facilitated the expansion of the human cortex may also render our species more susceptible to certain rare neurodevelopmental disorders.
Creative Minds: Programming Cells to Write Their Own Memoirs
Posted on by Dr. Francis Collins
Credit: Elowitz and Cai Labs, Caltech, Pasadena, CA
One of the most fascinating challenges in biology is understanding how a single cell divides and differentiates to form a complex, multicellular organism. Scientists can learn a lot about this process by tracking time-lapse images through a microscope. But gazing through a lens has its limitations, especially in the brain and other opaque and inaccessible tissues and organs.
With support from a 2017 NIH Director’s Transformative Research Program, a California Institute of Technology (Caltech) team now has a way around this problem. Rather than watching or digging information out of cells, the team has learned how to program cells to write their own molecular memoirs. These cells store the information right in their own genomic hard drives. Even better, that information is barcoded, allowing researchers to read it out of the cells without dissecting tissue. The programming can be performed in many different cell types, including stem or adult cells in tissues throughout the body.
Snapshots of Life: The Birth of New Neurons
Posted on by Dr. Francis Collins
Credit: Kira Mosher, University of California, Berkeley
After a challenging day at work or school, sometimes it may seem like you are down to your last brain cell. But have no fear—in actuality, the brains of humans and other mammals have the potential to produce new neurons throughout life. This remarkable ability is due to a specific type of cell—adult neural stem cells—so beautifully highlighted in this award-winning micrograph.
Here you see the nuclei (purple) and arm-like extensions (green) of neural stem cells, along with nuclei of other cells (blue), in brain tissue from a mature mouse. The sample was taken from the subgranular zone of the hippocampus, a region of the brain associated with learning and memory. This zone is also one of the few areas in the adult brain where stem cells are known to reside.
Snapshots of Life: Growing Mini-Brains in a Dish
Posted on by Dr. Francis Collins
Credit: Collin Edington and Iris Lee, Department of Biomedical Engineering, MIT
Something pretty incredible happens—both visually and scientifically—when researchers spread neural stem cells onto a gel-like matrix in a lab dish and wait to see what happens. Gradually, the cells differentiate and self-assemble to form cohesive organoids that resemble miniature brains!
In this image of a mini-brain organoid, the center consists of a clump of neuronal bodies (magenta), surrounded by an intricate network of branching extensions (green) through which these cells relay information. Scattered throughout the mini-brain are star-shaped astrocytes (red) that serve as support cells.
Gene Editing: Gold Nanoparticle Delivery Shows Promise
Posted on by Dr. Francis Collins
About a month ago, I had the pleasure of welcoming the Juip (pronounced “Yipe”) family from Michigan to NIH. Although you’d never guess it from this photo, two of the Juip’s five children—9-year-old Claire and 11-year-old Jake (both to my left)—have a rare genetic disease called Friedreich’s ataxia (FA). This inherited condition causes progressive damage to their nervous systems and their hearts. No treatment currently exists for kids like Claire and Jake, yet this remarkable family has turned this serious health challenge into an opportunity to raise awareness about the need for biomedical research.
One thing that helps keep the Juips optimistic is the therapeutic potential of CRISPR/Cas9, an innovative gene editing system that may someday make it possible to correct the genetic mutations responsible for FA and many other conditions. So, I’m sure the Juips were among those encouraged by the recent news that NIH-funded researchers have developed a highly versatile approach to CRISPR/Cas9-based therapies. Instead of relying on viruses to carry the gene-editing system into cells, the new approach uses tiny particles of gold as the delivery system!
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