Stem Cell Roundup: Artificial Embryos to Study Miscarriage and ALS Insight – Muscle Repair Cells Go Rogue

Stem Cell Image of the Week: Artificial embryos for studying miscarriage (Adonica Shaw)

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Mouse embryos artificially generated by combining three types of stem cells.
Image: University of Cambridge.

This week’s stem cell image of the week comes from a team of researchers from The University of Cambridge who published research in Nature Cell Biology earlier this week indicating they’d achieved a breakthrough in stem cell research that resulted in the generation of a key developmental step that’d never before been achieved when trying to generate an artificial embryo.

To create the artificial embryo, the scientists combined mouse embryonic stem cells with two other types of stem cells that are present in the very earliest stages of embryo development. The reseachers grew the three stem cell types into a dish and coaxed them into simulating a process called gastrulation – one of the very first events that happens during a creature’s development in which the early embryo begins reorganizing into more and more complex multilayer organ structures.

In an interview with The Next Web (TNW), Professor Magdalena Zernicka-Goetz, who led the research team, says:

”Our artificial embryos underwent the most important event in life in the culture dish. They are now extremely close to real embryos. To develop further, they would have to implant into the body of the mother or an artificial placenta.”

The goal of this research isn’t to create mice on demand. Its purpose is to gain insights into early life development. And that could lead to a giant leap in our understanding of what happens during the period in a woman’s pregnancy where the risk of miscarriage is highest.

According to professor Zernicka-Goetz,

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Magdalena Zernicka-Goetz, PhD

“We can also now try to apply this to the equivalent human stem cell types and so study the very earliest events in human embryo development without actually having to use natural human embryos.The early stages of embryo development are when a large proportion of pregnancies are lost and yet it is a stage that we know very little about. Now we have a way of simulating embryonic development in the culture dish, so it should be possible to understand exactly what is going on during this remarkable period in an embryo’s life, and why sometimes this process fails.”

Muscle repair cells go rogue – a possible drug target for ALS?
Call it a case of a good cell gone bad. This week researchers at Sanford Burnham Prebys Medical Discovery Institute, report in Nature Cell Biology that fibro-adipogenic progenitors (FAPs) – cells that are critical in coordinating the repair of torn muscles – can turn rogue, causing muscles to wither and scar. This “Dr. Jekyl and Mr. Hype” discovery may lead to novel treatments for a number of incurable disorders like amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal cord injury.

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Senior author Pier Lorenzo Puri, M.D. (right) and co-first author Luca Madaro, Ph.D. Credit: Fondazione Santa Lucia IRCCS

When muscle is strained, whether due to an acute injury or even weight-lighting, a consistent order of events occurs within the muscle. FAB cells enter the muscle tissue after immune cells called macrophages come in and gobble up dead tissue but before muscle stem cells are stimulated to regenerate the lost muscle. However, to the researchers’ surprise, something entirely different happens in the case of neuromuscular disorders like ALS where nerve signal connections to the muscles degenerate.

Once nerves are no longer attached to muscle and stop sending movement signals from the brain, the macrophages don’t infiltrate the muscle and instead the FAPs pile up in the muscle and never leave. And as a result, muscle stem cells are never activated. In ALS patients, this cellular train crash leads to progressive loss of muscle control to move the limbs and ultimately even to breathe.

The promising news from these findings, which were funded in part by CIRM, is that the team identified of an out-of-whack cell signaling pathway that is responsible for the breakdown in the rogue function of the FAP cells. The researchers hope further studies of this pathway’s role in muscle degeneration may lead to novel therapies and disease-screening technologies for ALS and other motor neuron diseases.

One thought on “Stem Cell Roundup: Artificial Embryos to Study Miscarriage and ALS Insight – Muscle Repair Cells Go Rogue

  1. Artificial Embryos to Study Miscarriage. Experimental study to generate an artificial embryo in vitro by combining mouse embryonic stem cells with other types of stem cells in the very earliest stages of embryo development. This is followed by coaxing them into the process of gastrulation. The early embryo is beginning reorganizing into more complex multi-layer of organ structure, which is extremely close to real embryo. Then, the embryo is implanted into the body of mother of mouse to observe the risk factors cause the pregnant women become miscarriage.

    Stem cell is multipotent cell to generate many types of functioning and specialized cells. The earliest embryonic stem cell is more powerful to develop into more specified cell types than the late stage of embryonic stem cell. As mention earlier, stem cell need growth factors to trigger the signaling of cell growth , gene expression and differentiation . Thus the late stages of embryonic stem cell are more well developed than earlier stage, due to turning on of many specific genes. Therefore, the selection of more earliest stages of stem cells provide the highest possibility to grow as embryo like structure, but this phenomena doesn’t occur in late stages of embryonic stem cell. Here, it is important to stress that, many factors do contribute the event of miscarriage in women. The status of health, ages, internal and external factor. The errors in earlier embryo development is not the sole factor to cause miscarriage. As we do see the deformed babies are born by women. The observation of stem cell study in miscarriage can be more complicated and confused. As evidence proved that progenitors of heart cells can be grow and differentiated into other types of specific cells.

    Muscle Repair Cells Go Rogue-A possible drug target for ALS. Fibro-adipogenic progenitors(FAPs) are critical in coordinating the repair of torn muscle to prevent the muscle becomes rogue, wither and scar. When the muscle is strained, a consistent order of events take place within the muscle. FAP cells enter the area of muscle tissue after the macrophages come and gobble up dead tissue. The muscle stem cells are stimulated to regenerate the lost muscle.

    In neuromuscular disorders like ALS, the lack of growth factors cause no nerve signaling and chemotractive response of macrophages to infiltrate to the site of muscle. Therefore, FAPs pile up in the muscle and the muscle stem cells are inactivated may lead to the loss of muscle to control the movement of limbs and breath in ALS patient. The study of growth factors treatment in human disease may aid additional advantages for stem cell therapy. The possibility of genetic deficiency in growth factors signaling pathway has to be carefully scrutinized.

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