Stories that caught our eye: FDA grants orphan drug status to CIRM-funded therapy; stunning discovery upends ideas of cell formation; and how tadpoles grow new tails

Gut busting discovery

Intestinal stem cells: Photo courtesy Klaus Kaestner, Penn Institute for Regenerative Medicine

It’s not often you read the word “sensational” in a news release about stem cells. But this week researchers at the University of Copenhagen released findings that are overturning long-held ideas about the development of cells in our stomachs. So perhaps calling it “sensational” is not too big a stretch.

In the past it was believed that the development of immature cells in our stomachs, before a baby is born, was predetermined, that the cells had some kind of innate sense of what they were going to become and when. Turns out that’s not the case. The researchers say it’s the cells’ environment that determines what they will become and that all cells in the fetus’ gut have the potential to turn into stem cells.

In the “sensational” news release lead author, Kim Jensen, says this finding could help in the development of new therapies.

“We used to believe that a cell’s potential for becoming a stem cell was predetermined, but our new results show that all immature cells have the same probability for becoming stem cells in the fully developed organ. In principle, it is simply a matter of being in the right place at the right time. Here signals from the cells’ surroundings determine their fate. If we are able to identify the signals that are necessary for the immature cell to develop into a stem cell, it will be easier for us to manipulate cells in the wanted direction’.

The study is published in the journal Nature.                             

A tale of a tail

African clawed frog tadpole: Photo courtesy Gary Nafis

It’s long been known that some lizards and other mammals can regrow severed limbs, but it hasn’t been clear how. Now scientists at the University of Cambridge in the UK have figured out what’s going on.

Using single-cell genomics the scientists were able to track which genes are turned on and off at particular times, allowing them to watch what happens inside the tail of the African clawed frog tadpole as it regenerates the damaged limb.

They found that the response was orchestrated by a group of skin cells they called Regeneration-Organizing Cells, or ROCs. Can Aztekin, one of the lead authors of the study in the journal Science, says seeing how ROCs work could lead to new ideas on how to stimulate similar regeneration in other mammals.

“It’s an astonishing process to watch unfold. After tail amputation, ROCs migrate from the body to the wound and secrete a cocktail of growth factors that coordinate the response of tissue precursor cells. These cells then work together to regenerate a tail of the right size, pattern and cell composition.”

Orphan Drug Designation for CIRM-funded therapy

Poseida Therapeutics got some good news recently about their CIRM-funded therapy for multiple myeloma. The US Food and Drug Administration (FDA) granted them orphan drug designation.

Orphan drug designation is given to therapies targeting rare diseases or disorders that affect fewer than 200,000 people in the U.S. It means the company may be eligible for grant funding toward clinical trial costs, tax advantages, FDA user-fee benefits and seven years of market exclusivity in the United States following marketing approval by the FDA.

CIRM’s President and CEO, Dr. Maria Millan, says the company is using a gene-modified cell therapy approach to help people who are not responding to traditional approaches.

“Poseida’s technology is seeking to destroy these cancerous myeloma cells with an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells.”

Poseida’s CEO, Eric Ostertag, said the designation is an important milestone for the company therapy which “has demonstrated outstanding potency, with strikingly low rates of toxicity in our phase 1 clinical trial. In fact, the FDA has approved fully outpatient dosing in our Phase 2 trial starting in the second quarter of 2019.”

Organoids revolutionize approach to studying a variety of diseases

Organoids

There are limitations to studying cells under a microscope. To understand some of the more complex processes, it is critical to see how these cells behave in an environment that is similar to conditions in the body. The production of organoids has revolutionized this approach.

Organoids are three-dimensional structures derived from stem cells that have similar characteristics of an actual organ. There have been several studies recently published that have used this approach to understand a wide scope of different areas.

In one such instance, researchers at The University of Cambridge were able to grow a “mini-brain” from human stem cells. To demonstrate that this organoid had functional capabilities similar to that of an actual brain, the researchers hooked it up to a mouse spinal cord and surrounding muscle. What they found was remarkable– the “mini-brain” sent electrial signals to the spinal cord that made the surrounding muscles twitch. This model could pave the way for studying neurodegenerative diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).

Spinal muscular atrophy

Speaking of SMA, researchers in Singapore have used organoids to come up with some findings that might be able to help people battling the condition.

SMA is a neurodegenerative disease caused by a protein deficiency that results in nerve degeneration, paralysis and even premature death. The fact that it mainly affects children makes it even worse. Not much is known how SMA develops and even less how to treat or prevent it.

That’s where the research from the A*STAR’s Institute of Molecular and Cell Biology (IMCB) comes in. Using the iPSC method they turned tissue samples from healthy people and people with SMA into spinal organoids.

They then compared the way the cells developed in the organoids and found that the motor nerve cells from healthy people were fully formed by day 35. However, the cells from people with SMA started to degenerate before they got to that point.

They also found that the protein problem that causes SMA to develop did so by causing the motor nerve cells to divide, something they don’t normally do. So, by blocking the mechanism that caused the cells to divide they were able to prevent the cells from dying.

In an article in Science and Technology Research News lead researcher Shi-Yan Ng said this approach could help unlock clues to other diseases such as ALS.

“We are one of the first labs to report the formation of spinal organoids. Our study presents a new method for culturing human spinal-cord-like tissues that could be crucial for future research.”

Just yesterday the CIRM Board awarded almost $4 million to Ankasa Regenerative Therapeutics to try and develop a treatment for another debilitating back problem called degenerative spondylolisthesis.

And finally, organoid modeling was used to better understand and study an infectious disease. Scientists from the Max Planck Institute for Infection Biology in Berlin created fallopian tube organoids from normal human cells. Fallopian tubes are the pair of tubes found inside women along which the eggs travel from the ovaries to the uterus. The scientists observed the effects of chronic infections of Chlamydia, a sexually transmittable infection. It was discovered that chronic infections lead to permanent changes at the DNA level as the cells age. These changes to DNA are permanent even after the infection is cleared, and could be indicative of the increased risk of cervical cancer observed in women with Chlamydia or those that have contracted it in the past.