Scientists "Program" Stem Cells to Begin Forming Dental Tissue
Researchers at the Faculty of Medicine at Masaryk University have succeeded in "programming" stem cells to transform into cells that form dental tissue. They directly intervened in the cells’ genome.
Understanding the processes behind the development of a functional organism is a fundamental prerequisite for being able to control and utilize them — for example, in regenerative medicine or tissue engineering. For Associate Professor Jan Křivánek, this has been a long-standing research focus. He was the first to describe in detail the development of odontoblasts — the cells that form the main hard dental tissue, dentin. Now, his team has managed to create these cells deliberately — by directly altering the genome of pluripotent stem cells, which are found at the very beginning of organism development and are capable of turning into any cell type found in the adult body.
“We identified four regulatory genes — genes that control the expression of other genes — and wanted to find out whether we could use them to prompt stem cells to transform into tooth-forming cells,” explains Jan Křivánek, head of the research group at the Institute of Histology and Embryology of the Faculty of Medicine, Masaryk University. Today, he can confirm the hypothesis as validated. The process, which began in vitro (by culturing cell lines “in a test tube”), was subsequently studied in vivo (in a living organism) in mice, into which the lab-modified cells were implanted. It turned out that even in mice, these artificially modified stem cells developmentally differentiated into dental tissue-forming cells — bringing the experiment closer to what happens in a living organism.
The innovative approach by the Brno scientists lies in how they influenced the stem cells. While most similar projects expose the cells to external factors, Křivánek and his colleagues intervened directly inside the genome. They used so-called lentiviruses — a group of retroviruses capable of causing chronic diseases in humans (such as HIV), characterized by a long incubation period. “What’s essential for us is that these viruses can integrate their DNA permanently into the host,”Křivánek explains, and adds: “They have the capacity to carry foreign genetic information — the so-called cargo space — into which we inserted the selected regulatory gene sequence. We used the resulting virion to infect the stem cells and thereby introduced the necessary genetic information into their genome.”
With these infected cells, the researchers gradually “switched on” the four selected regulatory genes, trying to find a combination that would lead to the transformation of stem cells into odontoblasts. “In the early phase, the cells began expressing genes characteristic of odontoblasts. Then they started producing collagen, and we later observed that they were also capable of forming mineralized deposits via calcium accumulation,”explains Mgr. Josef Lavický, Křivánek’s PhD student and the first author of the study, which has just been published in the Journal of Dental Research. A similar process occurs in the formation of bones or tooth enamel — generally in the development of hard tissues.
According to the researchers, the study could open new pathways not only in dental regenerative medicine. More broadly, it demonstrates a new method of deriving different cell types — various functional cells from stem cells. “We focused on odontoblasts, but I believe that if an appropriate combination of transcription factors — i.e., other regulatory genes — is carefully selected, it should be possible to derive other cell types similarly, whether epithelial cells or even neurons,” Křivánek anticipates.
Czech scientists “program” stem cells to produce dental tissue
Researchers at Masaryk University’s Faculty of Medicine have discovered a way to prompt stem cells to form dental tissue. Led by Jan Křivánek, the team used lentiviruses—retroviruses capable of permanently inserting their DNA into host cells—to introduce genetic information directly into the cells’ genome.
Once “infected,” the stem cells began behaving like those producing dentin, creating collagen and calcium deposits, key components of tooth structure. The breakthrough could pave the way for new approaches in regenerative dentistry, and the method may also be applied to generate other cell types for medical use.
