Stem Cell-Derived Dental Enamel Holds Potential for Tooth Regeneration

USA: Researchers from the University of Washington in Seattle have achieved a significant milestone by creating organoids from stem cells that can secrete dental enamel proteins, a crucial substance that safeguards teeth against damage and decay. 

This breakthrough holds the potential to pave the way for stem cell-based treatments aimed at repairing damaged teeth and even regenerating lost ones.

Leap Forward in Dental Restoration

The pioneering effort, led by a multi-disciplinary team of scientists, marks a critical first step towards a lofty goal: the development of innovative stem cell-based solutions for restoring damaged teeth and replenishing those that have been lost. 

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Hai Zhang, a co-author of the research paper and a professor of restorative dentistry at UW School of Dentistry, highlighted the significance of this achievement.

The research findings have been published in the journal Developmental Cell. The lead author of the paper is Ammar Alghadeer, a graduate student from Hannele Ruohola-Baker’s laboratory at the Department of Biochemistry in the UW School of Medicine. The laboratory is associated with the UW Medicine Institute for Stem Cell and Regenerative Medicine.

Unlocking the Genetic Program

Tooth enamel is a vital protective layer that shields teeth from the rigours of chewing and defends against decay. As the hardest tissue in the human body, enamel plays a pivotal role in dental health.

Creating ameloblasts, specialised cells responsible for producing enamel, in a laboratory setting necessitated understanding the genetic processes that steer fetal stem cells towards becoming these highly specialised enamel-producing cells. To decipher this genetic program, researchers employed a technique called single-cell combinatorial indexing RNA sequencing (sci-RNA-seq), which sheds light on the genes active at various developmental stages of a cell.

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Blueprint for Building Ameloblasts

With the help of sci-RNA-seq, researchers garnered snapshots of gene activation during different stages of human tooth development. By utilising an advanced computer program named Monocle, they then constructed a predictive trajectory of gene activities as undifferentiated stem cells metamorphosed into fully specialised ameloblasts.

Equipped with this trajectory, researchers succeeded in coaxing undifferentiated human stem cells into ameloblasts through exposure to chemical signals. This sequence of signals mimicked the path identified by the sci-RNA-seq data. Collaboration with the UW Medicine Institute for Protein Design led to the creation of computer-designed proteins that bolstered the effects of chemical signals.

Glimpse into the Future

This groundbreaking research not only produced ameloblasts but also unveiled a novel cell type termed subodontoblast. This cell type is believed to be a precursor to odontoblasts, which are vital for tooth formation. By combining these cell types, researchers managed to generate three-dimensional mini-organs known as organoids. These structures resemble the patterns observed during human tooth development and secrete essential enamel proteins.

Looking forward, the research team aspires to refine the process, creating enamel that rivals the durability of natural teeth. This could potentially lead to applications where laboratory-created enamel is used to mend cavities and other dental defects. A more ambitious endeavour involves crafting “living fillings” that can grow and repair cavities, or even regenerating teeth entirely from stem cells.

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Century of Dental Innovation

The research team sees teeth as an ideal model for advancing stem cell therapies. Teeth, being smaller and less complex than other organs, offer an accessible arena for developing cutting-edge regenerative solutions. As Professor Hannele Ruohola-Baker states, “This may finally be the ‘Century of Living Fillings’ and human regenerative dentistry in general.”

The success of this endeavour was a result of collaboration across various institutions, including the UW School of Dentistry, UW Brotman Baty Institute, UW Allen School of Computer Science and Engineering, Seattle Children’s Research Institute, and more. Researchers from different disciplines contributed their expertise to make this breakthrough possible.