Clinical Research // Skeletal Stem Cells

Giuseppe Intini, DDS, PhD

Leveraging skeletal stem cells to foster bone regeneration.

When trying to solve problems of bone-related disorders and injuries observed in clinics, Giuseppe Intini, DDS, PhD, doesn’t take the research only to the lab—he takes it to space.

A periodontist and an associate professor in the Department of Periodontics and Preventive Dentistry at the University of Pittsburgh School of Dental Medicine, Intini and his lab examine the functions of skeletal stem cells—stem cells crucial for bone growth and repair. Specifically, the team explores the potential of skeletal stem cells to advance therapies in areas like bone regeneration, craniofacial malformations, periodontal regeneration and osteosarcoma.

In Nov. 2022, Intini and his team launched their research into space from Cape Canaveral, Florida, as part of a NASA-sponsored SpaceX mission to the International Space Station. But what insights can research in outer space provide regarding the potential of skeletal stem cells in regenerative therapies—especially when those therapies are on Earth?

Interestingly, astronauts experience bone density loss and subsequent bone fragility due to microgravity, similar to osteoporosis on Earth. This reduced bone density suggests that skeletal stem cells behave differently when not under the influence of gravity.

Intini’s research on this trip explored two key aspects: the effect of microgravity, or lack of gravity, on skeletal stem cell behavior and an evaluation of RevBio’s innovative bone adhesive called Tetranite. Tetranite has shown significant clinical promise on Earth, but whether it is effective without gravity remains unknown. “We are testing whether Tetranite works on Earth and in space to gauge its usefulness in long-term space explorations,” said Intini.

Back on Earth, Intini’s research continues to examine the functionality of skeletal stem cell reservoirs—sources of stem cells in bone—and their potential application in bone regeneration therapies. In a study published in the Proceedings of the National Academy of Sciences in April 2023, his research team showed how physical manipulations of the calvarial sutures in the skull can promote calvarial bone regeneration in a mouse model without using additional therapeutic aids. These sutures are the immovable joints connecting the cranial bones in the skull and are a reservoir of calvarial skeletal stem cells.

Describing the research, Intini explained, “Mechanically expanding the calvarial suture can increase the number of calvarial skeletal stem cells and facilitate the regeneration of a calvarial bone defect—even if the defect is located far from the suture.”

In collaboration with medical professionals at UPMC Hillman Cancer Center and with the support of Pittsburgh Cure Sarcoma, Intini’s lab also studies the spatial transcriptomics of human osteosarcoma tissue using 10x Genomics’ Visium technology.

Spatial transcriptomics allows researchers to overlap gene expression profiling with individual cells in the context of their location in a tissue sample. The results provide a colorful blueprint of biochemical messages, biological functions and cell type architecture within the tissue sample. “By overlapping these two, you can identify which cells, in which area, of the tissue are expressing what [genetic transcripts], and that is extremely interesting,” Intini said enthusiastically.

The lab is using this technology to increase our understanding of gene expression patterns in osteosarcoma and advance our knowledge of its pathology and treatment strategies.

Intini’s charge in pushing beyond the physical limits of scientific discovery is a testament to the influence that interdisciplinary collaboration and cutting-edge technology have on the future of health care. “I believe the future of our research, of all of us, has to be centered on this kind of interdisciplinary collaboration—it is only by collaborating that you can move forward,” said Intini.

 

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