Uncovered Stem Cell: The Underlying Factor of Early Skull Fusion in Infants

by Liam O'Connor
8 comments
craniosynostosis

Research from Weill Cornell Medicine has identified a previously undetected stem cell, known as DDR2+, as the cause of premature skull fusion in infants, a condition termed craniosynostosis. This breakthrough has the potential to expand treatment options beyond surgical interventions. The study illustrates how this newly discovered stem cell influences the fusion and growth of the flat bones in the skull. Credit for the conceptual image is attributed to Greenblatt lab, generated using AI by Midjourney.

Study Overview

The medical researchers at Weill Cornell Medicine have elucidated that craniosynostosis, characterized by the premature closing of the skull in newborns, is due to an abnormal increase in a hitherto unknown bone-forming stem cell, referred to as the DDR2+ stem cell. This revelation paves the way for the development of alternative treatment modalities beyond surgical means.

Craniosynostosis is generally a result of genetic mutations and affects approximately one in every 2,500 infants. If untreated, the condition can constrict brain growth and lead to abnormal neurological development. Complex cases may require multiple surgical interventions for correction.

Key Findings

Recently published in the scientific journal Nature, the research team conducted an exhaustive investigation into the changes occurring in the skulls of mice that carried one of the most frequently observed mutations in human cases of craniosynostosis. They found that this particular mutation triggered early skull fusion by causing the abnormal multiplication of a newly identified type of bone-forming stem cell—DDR2+ stem cell.

A fresh type of stem cell, implicated in disorders of premature skull fusion, was examined in detail, revealing that it is responsible for the cartilage found at the sites of skull fusion. Credit for the discovery goes to the Greenblatt lab.

“With this discovery, we can now contemplate treating craniosynostosis through means other than solely surgical interventions, by mitigating this anomalous stem cell activity,” stated Dr. Matt Greenblatt, the co-senior author of the study and an associate professor of pathology and laboratory medicine at Weill Cornell Medicine, as well as a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center.

The other co-senior author involved in the research was Dr. Shawon Debnath, a research associate in the Greenblatt lab.

In a 2018 study, also published in Nature, Drs. Debnath and Greenblatt, along with their colleagues, had initially discovered another type of bone-forming stem cell, named the CTSK+ stem cell, and postulated its role in causing craniosynostosis due to its presence in the upper part of the skull in mice.

Unexpected Outcomes and Future Prospects

In this most recent study, the researchers engineered mice with CTSK+ stem cells lacking one of the genes that, when dysfunctional, leads to craniosynostosis. Contrary to expectations, mutations in the CTSK+ stem cells led to their depletion at the sutures, leading to more complete skull fusion, according to Dr. Debnath.

This unforeseen result led the research team to hypothesize the existence of another kind of bone-forming stem cell that could be responsible for abnormal suture fusion. Through additional experimentation and thorough cellular analysis, they identified the DDR2+ stem cell as the primary factor behind the condition.

They also discovered that normally, CTSK+ stem cells inhibit the production of DDR2+ stem cells. However, when affected by craniosynostosis-related gene mutations, the CTSK+ cells die off, allowing DDR2+ cells to multiply abnormally.

In collaboration with specialists from both Weill Cornell Medicine and Columbia University, the team identified the human equivalents of DDR2+ and CTSK+ stem cells in craniosynostosis surgical samples, underlining the probable clinical significance of their murine findings.

The study suggests that aberrant proliferation of DDR2+ stem cells could be controlled by mimicking the inhibitory methods that CTSK+ cells employ, through secretion of a growth factor protein known as IGF-1, among other regulatory proteins.

“The application of IGF-1 over the affected area partially prevented skull fusion, offering a promising avenue for future treatments,” stated Dr. Seoyeon Bok, the study’s primary author and a postdoctoral researcher in the Greenblatt lab.

“We are contemplating the use of pharmacological treatments that inhibit DDR2+ stem cell activity, alongside surgical management, to possibly reduce the need for multiple surgeries or to improve surgical outcomes,” added Dr. Greenblatt.

Besides focusing on treatments, the research team is also exploring the existence of other bone-forming stem cell types in the skull.

“This investigation has unveiled a greater level of complexity within the skull than initially suspected, and we anticipate that this is only the tip of the iceberg in terms of different stem cell types involved,” concluded Dr. Greenblatt.

Citation

The complete study titled “A multi-stem cell basis for craniosynostosis and calvarial mineralization” was authored by a multidisciplinary team and published on 20th September 2023 in Nature. DOI: 10.1038/s41586-023-06526-2.

Frequently Asked Questions (FAQs) about craniosynostosis

What is the key discovery made by researchers at Weill Cornell Medicine?

The researchers have identified a previously unknown type of stem cell, named DDR2+, which is responsible for the premature fusion of the skull in infants, a condition known as craniosynostosis.

Who led the study and who were the key contributors?

The study was co-led by Dr. Matt Greenblatt and Dr. Shawon Debnath. Dr. Greenblatt is an associate professor of pathology and laboratory medicine at Weill Cornell Medicine and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center. Dr. Debnath is a research associate in the Greenblatt laboratory.

What is craniosynostosis?

Craniosynostosis is a condition where the bones in an infant’s skull fuse prematurely. This can lead to abnormal brain development if not surgically corrected. It occurs in approximately one in 2,500 babies.

What are the implications of this discovery for the treatment of craniosynostosis?

The identification of the DDR2+ stem cell opens the possibility for developing non-surgical treatment options. Researchers suggest that by blocking the abnormal activity of this stem cell, the condition could potentially be treated more effectively.

What was the previously identified stem cell related to craniosynostosis?

Before the discovery of DDR2+ stem cells, researchers had identified another type of bone-forming stem cell, known as the CTSK+ stem cell, which they suspected played a role in craniosynostosis.

Was the study conducted only on mice?

While the study’s experiments were initially conducted on mice, the researchers also collaborated with craniosynostosis surgeons and neurogeneticists to investigate these stem cells in human tissue. Human versions of DDR2+ and CTSK+ stem cells were found in samples from craniosynostosis surgeries.

How can DDR2+ stem cell activity be suppressed?

The study suggests that DDR2+ stem cells can be suppressed by mimicking the methods normally used by CTSK+ stem cells. The researchers found that CTSK+ stem cells achieve this suppression by secreting a growth factor protein called IGF-1.

What are the future research directions after this discovery?

The research team is now exploring other bone-forming stem cell populations in the skull to understand the complexity further. They are also looking into developing DDR2+ stem cell-suppressing drug treatments to be used alongside surgical management.

When and where was the study published?

The study was published on September 20, 2023, in the journal Nature. The DOI for the article is 10.1038/s41586-023-06526-2.

More about craniosynostosis

  • Weill Cornell Medicine Official Website
  • Nature Journal Publication
  • Information on Craniosynostosis from Medical Sources
  • Dr. Matt Greenblatt’s Research Profile
  • NewYork-Presbyterian/Weill Cornell Medical Center
  • Overview of Stem Cells in Medicine
  • Columbia University Vagelos College of Physicians and Surgeons
  • Introduction to IGF-1 and Its Functions in Cellular Growth

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8 comments

Jennifer S October 31, 2023 - 12:56 pm

The collaboration between surgeons, neurogeneticists and researchers here is what science should be all about! Cant wait to see where this leads.

Reply
Nina H October 31, 2023 - 5:01 pm

Hats off to Dr. Greenblatt and Dr. Debnath, really. This could be a game-changer in pediatric medicine.

Reply
Tom R October 31, 2023 - 10:08 pm

I got a friend whose kid has this condition. Gonna send this to him right away, he needs to see theres hope beyond surgeries.

Reply
Mike D October 31, 2023 - 10:34 pm

I wasnt so sure about stem cell research but stuff like this proves its worth every penny. really cool discovery.

Reply
James T November 1, 2023 - 3:08 am

Wow, this is huge! Can’t believe they’ve actually found a new stem cell that’s the culprit. I mean, think of the possibilities for treatment now.

Reply
Alex P November 1, 2023 - 3:33 am

Anyone knows when human trials might start? I mean, this is promising but still, a long way to go right?

Reply
Linda K November 1, 2023 - 3:39 am

Did they just stumble on this DDR2+ thing or was it a planned find? Either way, it’s super fascinating.

Reply
Sarah M November 1, 2023 - 8:28 am

So, if I got it right, they can now potentially treat craniosynostosis without surgery? That’s amazing, honestly.

Reply

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